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Sample records for castration

  1. [Human castration: historical notes].

    Science.gov (United States)

    Serarcangeli, C; Rispoli, G

    2001-01-01

    Human castration has been performed from early times for different reasons: to punish and revenge, to display one's religious fanaticism, to protect or to control women, for eunuchs' trade, for therapeutical purposes. In early modern times men were castrated to obtain sopranos voices, or for eugenic or racial reasons. Nowadays chemical castration is used as a therapeutic treatment or as a way to punish rape and other criminal behaviours. Castration is surgical or chemical act that may obviously cause serious physical and psychological consequences. PMID:12375586

  2. Surgical castration, coercion and ethics

    DEFF Research Database (Denmark)

    Ryberg, Jesper; Petersen, Thomas Søbirk

    2014-01-01

    John McMillan's detailed ethical analysis concerning the use of surgical castration of sex offenders in the Czech Republic and Germany is mainly devoted to considerations of coercion.1 This is not surprising. When castration is offered as an option to offenders and, at the same time, constitutes...... the only means by which these offenders are likely to be released from prison, it is reasonable—and close to the heart of modern medical ethics—to consider whether the offer involves some kind of coercion. However, despite McMillan's seemingly careful consideration of this question, it appears to us...

  3. Acute Cold / Restraint Stress in Castrated Rats

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    Farideh Zafari Zangeneh

    2008-09-01

    Full Text Available Objective: The present study aimed to determine whether castration altered osmotically stimulated vasopressin (VP release and urinary volume and what is the role of endocrine-stress axis in this process.Materials and methods: Totally 108 mice were studied in two main groups of castrated (n=78 and control (n=30. Each group was extracted by acute cold stress (4◦C for 2h/day, restraint stress (by syringes 60cc 2h/day and cold/restraint stress. The castrated group was treated in sub groups of testosterone, control (sesame oil as vehicle of testosterone. Propranolol as blocker of sympathetic nervous system was given to both groups of castrated mice and main control.Results: Our results showed that, there is interactions between testosterone and sympathetic nervous system on vasopressin, because urine volume was decreased only in testoctomized mice with cold/restraint and cold stress (P<0.001; propranolol as the antagonist of sympathetic nervous system could block and increase urine volume in castrated mice. This increased volume of urine was due to acute cold stress, not restraint stress (p<0.001. The role of testosterone, noradrenalin (NA and Vasopressin (VP in the acute cold stress is confirmed, because testosterone could return the effect of decreased urine volume in control group (P<0.001. Conclusion: Considering the effect of cold/restraint stress on urinary volume in castrated mice shows that there is interaction between sex hormone (testosterone, vasopressin and adrenergic systems.

  4. Resource efficiency and economic implications of alternatives to surgical castration without anaesthesia

    NARCIS (Netherlands)

    Roest, de K.; Montanari, C.; Fowler, T.; Baltussen, W.H.M.

    2009-01-01

    This paper presents an analysis of the economic implications of alternative methods to surgical castration without anaesthesia. Detailed research results on the economic implications of four different alternatives are reported. castration with local anaesthesia, castration with general anaesthesia,

  5. Delayed physeal closure associated with castration in cats

    International Nuclear Information System (INIS)

    Radiographs of 152 cats under four years of age were examined for evidence of physeal closure. Radiographic closure was compared between entire male, castrated male, and female (neutered and entire] cats. Physeal closure in castrated males was delayed when compared to that of entire males

  6. [Castration of dogs from the standpoint of behaviour therapy].

    Science.gov (United States)

    Kuhne, F

    2012-04-24

    The castration of dogs is an amputation covered by Section 6 (1) of the Animal Protection Law in Germany. Apart from the general indications given by veterinary medicine, castration of an animal is a potential method of animal behaviour therapy. However, the highly variable, individual effects of castration on behaviour require detailed diagnosis by the veterinarian. Castration appears to exert its strongest influence on sexually dimorphic behaviour patterns in male dogs, e.g. status- related aggression, urine marking, mounting, house-soiling problems, and roaming. An indication to castrate a bitch is maternal aggression. When evaluating the effects of castration, one should always consider individual circumstances, such as learning experience (for example in the case of "experienced copulators"), age, and pack behaviour (if there is more than one dog in the household). Additional benefits of castration include a reduction in the dog's general activity level, decreased preparatory arousal and a decline in the dog's ability to focus its attention fully on the target of attack. As a result, it is much easier for the owner to disrupt and manage or control the dog's agonistic intentions. However, castration is not the ultimate remedy in dog-handling. Any decision in this respect should be based on a precise behaviour- related indication. Otherwise, such surgery may well violate the Animal Protection Law. PMID:22526819

  7. The hallmarks of castration-resistant prostate cancers.

    Science.gov (United States)

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

    2015-07-01

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

  8. Castration of a Black Rhinoceros Diceros Bicornis Minor

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    V de Vos

    1980-01-01

    Full Text Available A black rhinoceros (Diceros bicornis minor in the Addo Elephant National Park was castrated in order to prevent the possibility of an aotic inducing gene to be introduced into the Addo population. The classic castration technique was used. It was subsequently found that the rhino showed a drastic change in behaviour, and is at this stage predictably timid, which is not the case with his testis carrying compeers.

  9. Early and delayed castrations confer a similar survival advantage in TRAMP mice

    Institute of Scientific and Technical Information of China (English)

    Zai-Xian Zhang; Qing-Quan Xu; Xiao-Bo Huang; Ji-Chuan Zhu; Xiao-Feng Wang

    2009-01-01

    The most appropriate time to introduce androgen deprivation therapy for prostate cancer remains controversial. Our aim was to evaluate the effects of early versus delayed surgical castration on prostate cancer progression and survival in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice were randomly divided into three groups: the early castration group (on which castration was performed at the age of 4 weeks), the delayed castration group (on which castration was performed when abdominal turnouts could be palpated), and the sham-castrated group. Mice were monitored daily throughout their lives until cancer-related death or the develop-ment of an obviously moribund appearance, at which time the individual mouse was killed. Androgen receptor expression in prostate turnouts was also evaluated. The results shows that the average lifespan in early castration, delayed castration and sham-castrated groups were 54.1 weeks, 59.9 weeks and 39.1 weeks, respectively. Both early castration and delayed castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P<0.001). However, the difference in lifespan between the early castration group and the delayed castration group was not statistically significant (P=0.85). The increase in lifespan in the TRAMP mice that received either early or delayed castration correlated with lower G/B value (genitourinary tract weight/body weight) at death than the sham-castrated mice. In conclusion, early and delayed castrations in TRAMP mice pro-longed survival to a similar extent. This finding may provide a guide for clinical practice in prostate cancer therapy.

  10. Enzalutamide for patients with metastatic castration-resistant prostate cancer

    Science.gov (United States)

    Ramadan, Wijdan H; Kabbara, Wissam K; Al Basiouni Al Masri, Hiba S

    2015-01-01

    Objective To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI®) in metastatic castration-resistant prostate cancer. Data sources Literature search was done through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration-resistant prostate cancer. Data from FDA product labels were also used. Study selection and data extraction Recent and relevant studies were included in the review. Collected clinical trials were screened and evaluated. Data synthesis Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and affinity to the AR. It was approved by the FDA to treat metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, after a Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this population. Recently, the FDA expanded the approval of enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not receive chemotherapy. Moreover, enzalutamide is shown to be associated with an acceptable safety profile. Conclusion Enzalutamide has been shown to be both safe and effective in improving overall survival in metastatic castration-resistant prostate cancer postchemotherapy with docetaxel and as a first line treatment before initiation of chemotherapy. However, additional studies and head-to-head trials are needed. PMID:25945058

  11. Castration, cult and agriculture : Perspectives on Greek animal sacrifice

    OpenAIRE

    Ekroth, Gunnel

    2014-01-01

    The castration of most male animals seems to have been the rule in ancient Greece when rearing cattle, sheep, goats, and pigs; only very few adult males are needed for breeding purposes and flocks of bulls, rams, billy-goats and boars are difficult to keep, since they are too aggressive. Castrated males yield more and fattier meat, and, in the case of sheep, more wool. Still, sacred laws and sacrificial calendars stipulate the sacrifice of uncastrated victims, and vase-paintings frequently re...

  12. Correlation between lipid, cholesterol and fatty acid contents in the shoulder of castrated and non-castrated Santa Inês lambs

    OpenAIRE

    Cristiane Leal dos Santos-Cruz; Christian Albert Carvalho da Cruz; Thiago Ramos Lima; Juan Ramon Olalquiaga Pérez; Rodrigo Soares Junqueira; Braulio Crisanto Carvalho da Cruz

    2012-01-01

    The objective of this study was to establish a correlation between the content of total lipids, cholesterol and fatty acid profile of the edible portion of the shoulders of 12 castrated and 12 non-castrated Santa Ines lambs, slaughtered at different ages (84, 168, 210, 252 days). Shoulders and the edible portion (muscle and fat) were weighed and stored at -5 °C. Castrated and uncastrated lambs increased their body weight and half carcass weight, respectively. The shoulder weight increased in ...

  13. Castration in male pigs: techniques and animal welfare issues.

    Science.gov (United States)

    Thun, R; Gajewski, Z; Janett, F

    2006-11-01

    Castration in male pigs is usually performed during the first weeks of life without prior anesthesia. This technique, however, is known to induce acute pain and stress and will therefore not be tolerated any longer by animal welfare organizations. Practical and animal-friendly alternatives to surgical castration are the production of entire male pigs, semen sexing or immunological castration. Fattening boars has the benefits of better feed efficiency, higher lean meat yield and increased animal welfare due to no pain and stress of castration. The most important disadvantage in raising entire male pigs is the incidence of boar taint ranging between 10 and 75%. To identify tainted carcasses an accurate and rapid on-line method for detection of odorous compounds is absolutely necessary. Sperm sexing through flow cytometry is the only commercially available method at the moment but speed of separation is too low for practical application. Active immunization of boars against gonadotropin-releasing-hormone (GnRH) at the end of the fattening period results in a significant reduction of testicular weight and androstenone production while the benefits of daily growth gain, meat quality as well as welfare remain the same as in entire males. In the present review more detailed information is given about the various techniques, especially the practical application of immunocastration on a large scale base. PMID:17242482

  14. Varieties of Castration Experience: Relevance to Contemporary Psychoanalysis and Psychodynamic Psychotherapy.

    Science.gov (United States)

    Taylor, Graeme J

    2016-03-01

    Although Freud considered castration to be one of the two major anxieties of human life, the castration complex has been relatively neglected in contemporary psychoanalytic writing and is insufficiently discussed in presentations of clinical cases. This article discusses the relevance of the concept to contemporary psychoanalysis and psychodynamic psychotherapy, in particular the important contributing role of castration conflicts in the pathogenesis of a wide range of clinical symptoms. The author begins by briefly reviewing some classical and contemporary psychoanalytic ideas about castration to show how the concept has broadened and is currently used not only to signify fear of damage to or loss of the genital, but also metaphorically to indicate a threat to or loss of any valued human characteristic or function. He outlines Brenner's distinction between castration anxiety and castration depression, and reviews the role of childhood trauma in intensifying castration conflicts. He then illustrates the clinical application of these ideas by describing aspects of his psychotherapeutic work with three male patients who presented with a variety of symptoms and distressing psychological experiences that were gradually resolved through the analysis of underlying castration anxiety and/or castration depression. Although castration anxiety is frequently intermingled with separation anxiety, the author concludes that with many traumatized patients castration conflicts are in the foreground and the therapist needs to focus on the patient's proneness to humiliation, powerlessness, and shame. PMID:26938799

  15. Effect of local anaesthesia and/or analgesia on pain responses induced by piglet castration

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    Nyman Görel

    2011-05-01

    Full Text Available Abstract Background Surgical castration in male piglets is painful and methods that reduce this pain are requested. This study evaluated the effect of local anaesthesia and analgesia on vocal, physiological and behavioural responses during and after castration. A second purpose was to evaluate if herdsmen can effectively administer anaesthesia. Methods Four male piglets in each of 141 litters in five herds were randomly assigned to one of four treatments: castration without local anaesthesia or analgesia (C, controls, analgesia (M, meloxicam, local anaesthesia (L, lidocaine, or both local anaesthesia and analgesia (LM. Lidocaine (L, LM was injected at least three minutes before castration and meloxicam (M, LM was injected after castration. During castration, vocalisation was measured and resistance movements judged. Behaviour observations were carried out on the castration day and the following day. The day after castration, castration wounds were ranked, ear and skin temperature was measured, and blood samples were collected for analysis of acute phase protein Serum Amyloid A concentration (SAA. Piglets were weighed on the castration day and at three weeks of age. Sickness treatments and mortality were recorded until three weeks of age. Results Piglets castrated with lidocaine produced calls with lower intensity (p p p = 0.06, n.s. and the following day (p = 0.02. Controls had less swollen wounds compared to piglets assigned to treatments M, L and LM (p p = 0.005; p = 0.05 for C + L compared to M + LM. Ear temperature was higher (p Conclusions The study concludes that lidocaine reduced pain during castration and that meloxicam reduced pain after castration. The study also concludes that the herdsmen were able to administer local anaesthesia effectively.

  16. Castration of piglets under general anaesthesia: a possible approach

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    Iwan Nussbaumer

    2012-05-01

    Full Text Available Since January 2010 the castration of piglets without pain relief has been forbidden in Switzerland. Swiss pig farmers now have two choices, either vet-performed anaesthesia and analgesia by intramuscular injection or farmer-administered isofluran anaesthesia by an inhalation device. Many smaller pig producers, with less than 60 sows, have chosen injected anaesthesia for economic, user safety and environmental reasons.

  17. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    OpenAIRE

    Ömer Acar; Tarık Esen; Lack, Nathan A.

    2013-01-01

    Hindawi Publishing Corporation The ScientificWorld Journal Volume 2013, Article ID 379641, 8 pages http://dx.doi.org/10.1155/2013/379641 Review Article New Therapeutics to Treat Castrate-Resistant Prostate Cancer Ömer Acar,1 TarJk Esen,1,2 and Nathan A. Lack1 1 VKF American Hospital, Guzelbahce sokak, Nisantasi, Istanbul 34365, Turkey 2 School of Medicine, Koc¸ University, Rumelifeneri Yolu, Sariyer, Istanbul 34450, Turkey Correspondence should be addressed to Natha...

  18. Castration-resistant prostate cancer: systemic therapy in 2012

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    Fernando C. Maluf

    2012-01-01

    Full Text Available Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

  19. Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Sharp, Adam; Welti, Jonathan; Blagg, Julian; de Bono, Johann S

    2016-09-01

    Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280-2. ©2016 AACRSee related article by Yang et al., p. 4466.

  20. Quality Characteristics and Composition of the Longissimus Muscle from Entire and Castrate Elk in Korea.

    Science.gov (United States)

    Kim, Sang-Woo; Kim, Kwan-Woo; Park, Seong-Bok; Kim, Myung-Jick; Yim, Dong-Gyun

    2016-05-01

    The objective of the research was to determine the chemical composition as well as the physicochemical properties of the longissimus muscle from Korean entire and castrate elk. Twelve elk stags were raised and fed on concentrate with ad libitum hay. All animals were equally divided into castrated and non-castrated (entire) males, and slaughtered at 5 year of age. It was found that entire elk, in comparison with castrate elk, had higher content of moisture and lower content of fat (pumami taste. It is apparent that the castrate animals carried higher content of histidine, isoleucine, and leucine than those of the entire group (p<0.05). In this study, it was concluded that venison quality of elk is affected by castration and these results can provide fundamental information for venison production. PMID:26954142

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

    Science.gov (United States)

    Silvani, Mauro; Mondaini, Nicola; Zucchi, Alessandro

    2015-09-01

    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.

  2. The first experience in using abiraterone acetate in patients with castration-refractory prostate cancer

    OpenAIRE

    L. M. Rapoport; E. A. Bezrukov; A. V. Kondrashina

    2015-01-01

    Even in the mid-twentieth century, Huggins and Hodges proved the susceptibility of prostate cancer cells to hormonal manipulations, by using surgical castration as an example. An average of 18–36 months after initiation of first-line hormonal therapy, patients develop the castration resistance in prostate cancer, one of the causes of which was hyperproduction of the tumor receptors of prostate cancer cells and their hypersusceptibility to the castration levels of testosterone. Long-term treat...

  3. CYP17A1 Inhibitors in Castration-Resistant Prostate Cancer

    OpenAIRE

    Gomez, Lissette; Jason R Kovac; Dolores J Lamb

    2015-01-01

    The majority of prostate cancer (PCa) cases are diagnosed as a localized disease. Definitive treatment, active surveillance or watchful waiting are employed as therapeutic paradigms. The current standard of care for the treatment of metastatic PCa is either medical or surgical castration. Once PCa progresses in spite of castrate androgen levels it is termed ‘castration-resistant prostate cancer’ (CRPC). Patients may even exhibit rising PSA levels with possible bone, lymph node or solid organ ...

  4. Correlation between lipid, cholesterol and fatty acid contents in the shoulder of castrated and non-castrated Santa Inês lambs

    Directory of Open Access Journals (Sweden)

    Cristiane Leal dos Santos-Cruz

    2012-07-01

    Full Text Available The objective of this study was to establish a correlation between the content of total lipids, cholesterol and fatty acid profile of the edible portion of the shoulders of 12 castrated and 12 non-castrated Santa Ines lambs, slaughtered at different ages (84, 168, 210, 252 days. Shoulders and the edible portion (muscle and fat were weighed and stored at -5 °C. Castrated and uncastrated lambs increased their body weight and half carcass weight, respectively. The shoulder weight increased in the carcasses of uncastrated animals. The edible portion of the shoulders of castrated lamb has greater amount of total lipids (16.09 g/100 g. The cholesterol content was influenced by castration, reducing with age. Santa Ines castrated lambs, under semi-extensive conditions, presented larger amounts of C18:1 T11 and CLA in the edible portion of the shoulder. Castration causes no significant correlation between total lipids, cholesterol and total saturated and unsaturated fatty acids of the edible portion of Santa Ines shoulder lambs from 84 to 252 days of age.

  5. Effect of tasting and information on consumer opinion about pig castration

    NARCIS (Netherlands)

    Kallas, Z.; Gil, J.M.; Panella-Riera, N.; Blanch, M.; Furnols, M.F.I.; Chevillon, P.; Roest, de K.; Tacken, G.M.L.; Oliver, M.A.

    2013-01-01

    Our research explored the relative importance of pig castration amongst other aspects of animal welfare, and the potential impact of information and sensory experiences on European Union (EU) consumers' preferences. The EU is considering a future ban on surgical pig castration by 2018 which may affe

  6. Empirical support for optimal virulence in a castrating parasite.

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    Knut Helge Jensen

    2006-07-01

    Full Text Available The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times

  7. Abiraterone Acetate and Castration Resistant Ductal Adenocarcinoma of the Prostate

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    Edgar Linden-Castro

    2014-01-01

    Full Text Available Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate.

  8. EXPERIENCE WITH OCTREOTIDE IN PATIENTS WITH CASTRATION REFRACTORY PROSTATE CANCER

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    D. I. Ganov

    2014-07-01

    Full Text Available Fifteen patients with castration refractory prostate cancer have been treated with sustained-release octreotide in combination with dexamethasone at the Altai Territory Oncology Dispensary since 2008. Control PSA test revealed that 9 (60 % patients had positive changes; tumor process stabilization was noted in 4 (26.7 % and only 2 (13.3 % were found to have disease progression. Thus, more than 86 % of patients responded to combination treatment with sustained-release octreotide + dexamethasone. Octreotide treatment caused no serious specific adverse toxic reactions.

  9. Castration modulates singing patterns and electrophysiological properties of RA projection neurons in adult male zebra finches

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    Songhua Wang

    2014-04-01

    Full Text Available Castration can change levels of plasma testosterone. Androgens such as testosterone play an important role in stabilizing birdsong. The robust nucleus of the arcopallium (RA is an important premotor nucleus critical for singing. In this study, we investigated the effect of castration on singing patterns and electrophysiological properties of projection neurons (PNs in the RA of adult male zebra finches. Adult male zebra finches were castrated and the changes in bird song assessed. We also recorded the electrophysiological changes from RA PNs using patch clamp recording. We found that the plasma levels of testosterone were significantly decreased, song syllable’s entropy was increased and the similarity of motif was decreased after castration. Spontaneous and evoked firing rates, membrane time constants, and membrane capacitance of RA PNs in the castration group were lower than those of the control and the sham groups. Afterhyperpolarization AHP time to peak of spontaneous action potential (AP was prolonged after castration.These findings suggest that castration decreases song stereotypy and excitability of RA PNs in male zebra finches.

  10. Pre-pubertal castration improves spatial learning during mid-adolescence in rats.

    Science.gov (United States)

    Moradpour, Farshad; Naghdi, Nasser; Fathollahi, Yaghoub; Javan, Mohamad; Choopani, Samira; Gharaylou, Zeinab

    2013-10-01

    Hippocampus functions, including spatial cognition and stress responses, mature during adolescence. In addition, hippocampus neuronal structures are modified by circulating sex steroids, which dramatically increase during adolescence. Therefore, the effects of castration and the circulating levels of the main sex steroid testosterone on spatial learning and memory were examined across postnatal ages to test whether pre-pubertal castration affected rats' spatial ability in the Morris Water maze (MWM). Male rats were either castrated or sham-castrated at 22d (days of age), or left gonadally intact. They were then trained and tested in the MWM beginning at 28d, 35d, 45d or 60d. We found that all of the intact rats learned the spatial task; however, the males at 22d and 28d required more trials to acquire the task than the males at older ages. The males castrated at 22d and tested at 35d had significantly lower escape latency and traveled distance during training than the sham-castrated males trained at the same age. No differences were observed in mean values of escape latency and traveled distance at 45d even though they had comparable levels of testosterone. We conclude that adult-typical performance for male spatial memory emerges during mid-adolescence and that pre-pubertal castration appears to improve spatial learning during this time. PMID:23871792

  11. Total antiradical activity in male castrated piglets blood: reference values

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    Carlo Corino

    2010-01-01

    Full Text Available Blood samples from 146 male castrated piglets in the range of 10-47kg body weight were collected from the same farm and analysed for total antiradical activity in order to determine reference intervals. Data were tested for normality and then submitted to reference limit evaluation. The reference values found in piglets, expressed as half-hemolysis time (59.34 – 93.60 and 43.94 – 66.90 minutes for blood and red blood cell, respectively, are lower than those found in humans; further studies are needed to extend reference values study to female and to animals of different weight classes and different genetic type.

  12. Comparative proteomic analysis of longissimus dorsi muscle in immuno- and surgically castrated male pigs.

    Science.gov (United States)

    Shi, Xuebin; Li, Chunbao; Cao, Miaodan; Xu, Xinglian; Zhou, Guanghong; Xiong, Youling L

    2016-05-15

    We compared proteomic profiles of male pig muscles after active immunization against gonadotropin releasing hormone (GnRH) and surgical castration. Longissimus dorsi samples were collected from immunocastration (IC) and surgical castration (SC) groups (n=15 each). Muscle proteins were extracted and then identified by data-independent label-free nano LC-MS/MS. A total of 610 proteins were identified, 50 of which were differentially expressed (P<0.05) between immuno- and surgical castration. Twenty-two of 50 differentially expressed proteins were higher in abundance for IC group and 27 proteins with abundance change folds greater than 1.5 differed with castration methods. Proteins involved in cytoskeleton and immunity were abundant in IC group. Several heat shock proteins (HSPs) and laminins were abundant in SC group.

  13. Experimental Evidence of Persistent Androgen-Receptor-Dependency in Castration-Resistant Prostate Cancer

    OpenAIRE

    Osamu Ogawa; Tomomi Kamba; Takahiro Inoue; Takashi Kobayashi

    2013-01-01

    In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent subli...

  14. Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Steven Kregel

    Full Text Available Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR, has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5 expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

  15. Temporal patterns of inflammatory gene expression in local tissues after banding or burdizzo castration in cattle

    Directory of Open Access Journals (Sweden)

    Sweeney Torres

    2009-09-01

    Full Text Available Abstract Background Castration of male cattle has been shown to elicit inflammatory reactions and acute inflammation is initiated and sustained by the participation of cytokines. Methods Sixty continental × beef bulls (Mean age 12 ± (s.e. 0.2 months; Mean weight 341 ± (s.e. 3.0 kg were blocked by weight and randomly assigned to one of three treatments (n = 20 animals per treatment: 1 untreated control (Con; 2 banding castration at 0 min (Band; 3 Burdizzo castration at 0 min (Burd. Samples of the testis, epididymis and scrotal skin were collected surgically from 5 animals from each group at 12 h, 24 h, 7 d, and 14 d post-treatment, and analysed using real-time PCR. A repeated measurement analysis (Proc GLM was performed using SAS. If there was no treatment and time interaction, main effects of treatment by time were tested by ANOVA. Results Electrophoresis data showed that by 7 d post-castration RNA isolated from all the testicle samples of the Burd castrated animals, the epididymis and middle scrotum samples from Band castrates were degraded. Transitory effects were observed in the gene expression of IFN-γ, IL-6, IL-8 and TNF-α at 12 h and 24 h post treatment. Burd castrates had greater (P Conclusion Banding castration caused more inflammatory associated gene expression changes to the epididymis and scrotum than burdizzo. Burdizzo caused more severe acute inflammatory responses, in terms of pro-inflammatory cytokine gene expression, in the testis and epididymis than banding.

  16. Castration Therapy of Prostate Cancer Results in Downregulation of HIF-1{alpha} Levels

    Energy Technology Data Exchange (ETDEWEB)

    Al-Ubaidi, Firas L.T. [Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm (Sweden); Department of Urology, Central Hospital, Vaesteras (Sweden); Schultz, Niklas [Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm (Sweden); Egevad, Lars [Department of Oncology-Pathology, Karolinska Institutet, Stockholm (Sweden); Granfors, Torvald [Department of Urology, Central Hospital, Vaesteras (Sweden); Helleday, Thomas, E-mail: helleday@gmt.su.se [Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm (Sweden); Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Science for Life Laboratory, Stockholm University, Solna (Sweden)

    2012-03-01

    Background and Purpose: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. Methods and Materials: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in cancer was determined by immunofluorescence. Results: Among biopsy specimens taken before castration, strong HIF-1{alpha} expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1{alpha} (mean intensity 0-10) in 6 patients. Downregulation of HIF-1{alpha} expression after castration was observed in all 5 patients with strong HIF-1{alpha} precastration expression. HIF-1{alpha} expression was also reduced in 2 of 3 patients with weak HIF-1{alpha} precastration expression. Conclusions: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.

  17. Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Abeer A.Mahmoud; Eman A.El-Sharawy; Mohamed M.El-Bassiouny; Ramy R.Ghali

    2014-01-01

    Objective: Maximum androgen blockade (MAB), consisting of an antiandrogen plus either a luteinizing hormone-releasing hormone agonist (LHRHA) or orchiectomy, is a standard care for patients with prostate cancer. Although, clinical trial results have been equivocal, none has shown a significant advantage in favor of MAB over castration alone in metastatic prostate cancer and MAB has been the subject of considerable controversy. The aim of this study was to compare MAB (orchiectomy or LHRHA “Goserelin”) and anti-androgen “Bicalutamide” with castration alone (orchiectomy or LHRHA) in previ-ously untreated metastatic prostate cancer patients.Methods: Hundred eligible patients with adequate performance status and adequate hematologic, hepatic and renal functions were included. MAB arm, fifty patients underwent castration either surgicaly by orchiectomy or medicaly by receiving Goserelin (3.6 mg) depot, which was injected subcutaneously every 28 days plus bicalutamide 50 mg once daily. Castration alone arm, fifty patients underwent castration alone either surgicaly by orchiectomy or medicaly by receiving Goserelin (3.6 mg) depot.Results: During the period from January 2011 to January 2013, with a median folow up of 18 months (range 6 to 24 months), there were eight deaths (16%), in MAB arm and ten deaths (20%) in castration alone arm. At three months, there were 35 patients (70%) with prostate specific antigen (PSA) normalization (≤ 4 mg/dL) in MAB arm versus 17 patients (34%) with PSA normalization in castration alone arm (P = 0.001). The median progression free survival (PFS) times were 22.18 months (95% CI, 19.7 to 24.2 months) for MAB arm versus 22 months in castration alone arm (95% CI, 18 to 25.9 months;P = 0.045). The survival rates for MAB arm were 82% at 18 months and 70.6% at 24 months versus 78.7% at 18 months and 75.1% at 24 months in castration alone arm (P > 0.05). The median overal survival (OS) was not reached in either arm. Both hematological

  18. Effect of Surgical and Immunological Castration on Haematological Variables, Reproductive Hormones and Ejaculate Characteristics in Mongrel Dogs.

    Science.gov (United States)

    Ajadi, Temitope A; Gazal, Oladele S

    2016-01-01

    Welfare concerns are growing regarding surgical castration (SC) in pets, necessitating the need for non-surgical alternatives. Administration of vaccines against gonadotropins releasing hormone (GnRH) have been reported as alternative to SC. This study determined the effect of surgical and immunological castrations (IC) on complete blood counts, plasma testosterone (T), luteinizing hormone (LH) concentrations and ejaculate characteristics in mongrel dogs. Ten intact male dogs were randomly divided into two groups (A & B). Dogs in group A were surgically castrated, while dogs in group B were immunologically castrated with single subcutaneous injection of GnRH vaccine (Improvac®). Blood and semen were collected before SC or IC and fortnightly until sixteen weeks. Blood was analyzed for packed cell volume (PCV), white blood cell count (WBC), haemoglobin concentration (Hb), absolute neutrophil (NEUT) and lymphocyte counts (LYMP), T and LH. Sperm volume (SV), concentration (C), motility (SM), live-dead ratio (LDR) and percentage of abnormal spermatozoa were determined for the semen. Data were presented as mean ± standard deviation and compared using analysis of variance. The PCV and HB of dogs surgically castrated increased progressively up to16th week after castration but only up to10 weeks in dogs immunologically castrated. Both PCV and HB decreased progressively after 10 weeks in dogs immunologically castrated. Similarly, the WBC of dogs surgically castrated steadily increased from 2 weeks up to week 16, while it increased from 6 weeks up to 16 weeks in dogs immunologically castrated. However, PCV, Hb, WBC, NEUT and LYMP did not differ significantly (p > 0.05) between SC and IC. In both groups, the SV, SC, SM, LDR and percentage of abnormal spermatozoa did not differ significantly. It was therefore concluded that there is no significant haematological or endocrinological changes between surgical and immunological castration and that immunological castration may

  19. [Treatment of metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Caffo, Orazio

    2015-01-01

    The treatment of metastatic castration-resistant prostate cancer (mCRPC) represents one of the oncological fields where the most impressive improvements has been observed in the last decades. At the beginning of this century, the expected survival of mCRPC patients was not more than 12 months. After the introduction of docetaxel in the clinical practice in 2004, and the recent availability of new drugs cabazitaxel, abiraterone acetate, enzalutamide, and radium-223 the landscape is dramatically changed with an expected median survival of about three years. The possibility of administering docetaxel, abiraterone acetate, and enzalutamide as first line treatment, and cabazitaxel, abiretone acetate, and enzalutamide as second line, as well as the availability of radium-223 for the treatment of mCRPC patients regardless of chemotherapy administration, changed the natural history of the disease. At the same time, it is probable that also the biology of the disease is changing with the appearance of mechanisms of resistance which are common to all the drugs. This plays a central role in sequencing the available drugs not only in the first and second line setting but also beyond the second line. The future challenges for the oncologists will be to develop new drugs able to overcome the resistances, mainly when they are native, to find the optimal sequence to optimize the use of available drugs, to place at the best place other active drugs, such as vaccines and radiopharmaceuticals, to exploit the new drugs also in a hormone-sensitive phase. PMID:25621779

  20. Emerging targeted therapies for castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo eAdamo

    2012-05-01

    Full Text Available Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC. Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone and denosumab have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel hormone-therapeutic, intracellular molecular pathways inhibiting, anti-angiogenic, bone microenvironment targeting and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan. Optimal timing, right combination and/or sequencing of emerging therapies as well as use of more sensitive biological markers to individualize therapies for CRPC remain challenging and studies to investigate these aspects are needed.

  1. Radium-223 in metastatic castration resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Winston Vuong; Oliver Sartor; Sumanta K Pal

    2014-01-01

    In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival beneift in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors inlfuencing clinical implementation.

  2. Novel agents in the management of castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Shruti Chaturvedi

    2014-01-01

    Full Text Available Prostate cancer (PCa is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC. Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.

  3. Tpl2 induces castration resistant prostate cancer progression and metastasis.

    Science.gov (United States)

    Lee, Hye Won; Cho, Hyun Jung; Lee, Se Jeong; Song, Hye Jin; Cho, Hee Jin; Park, Min Chul; Seol, Ho Jun; Lee, Jung-Il; Kim, Sunghoon; Lee, Hyun Moo; Choi, Han Yong; Nam, Do-Hyun; Joo, Kyeung Min

    2015-05-01

    Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC. PMID:25274482

  4. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor; Silke Gillessen

    2014-01-01

    Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  5. A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu-hsiang LIN; Chien-lun CHEN; Chen-pang HOU; Phei-lang CHANG; Ke-hung TSUI

    2011-01-01

    Airn:To examine the outcomes of patients with advanced prostate carcinoma who underwent medical or surgical castration.Methods:A hundred twenty one consecutive cases of patients with advanced prostate carcinoma who underwent medicaI or surgical castration between 2001 and 2006 were retrospectively reviewed.Associations between clinicaI outcomes and prognostic scoring factors were determined based on the Reijke study.In the surgical and medical castration groups.the impact on the prostate-specific antigen(PSA)normalization rate,the rebound rate and the disease-free survivaI rate were evaluated.The mean foIlow-up was 36.1months.Results:In the initial 12 months.there were no statisticaI differences in the PSA normalization rate and the PSA rebound rate between the two groups.However,the PSA rebound rate after the 12th month(20.90%vs 40.74%.P=-0.0175)and the 18th month PSA normalization rate(59.70%vs 37.04%.P=0.0217)differed significantly between the two groups,and these differences were maintained to the end of the study.When comparing patients grouped according to Reijke prognosis scores.there was no difference between medical and surgical castration for the good prognosis group.However, among the patients given a poor prognosis,surgical castration was superior in terms of the PSA normalization rate,the PSA rebound rate.the tumor progression-free survival rate(P<0.001)and the overalI survivaI rate (P<0.001).Conclusion:Advanced prostate carcinoma patients with poor pretreatment prognosis scores should undergo surgical castration rather than medical castration for better PSA rebound rates and overaII survival.

  6. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth

    DEFF Research Database (Denmark)

    Jiang, Nan; Hjorth-Jensen, Kim; Hekmat, Omid;

    2015-01-01

    Prostate cancer remains a leading cause of cancer-related mortality worldwide owing to our inability to treat effectively castration-resistant tumors. To understand the signaling mechanisms sustaining castration-resistant growth, we implemented a mass spectrometry-based quantitative proteomic app...

  7. Effect of castration age on weight and size of some bones in Piemontese male cattle

    Directory of Open Access Journals (Sweden)

    C. Lazzaroni

    2010-04-01

    Full Text Available Effect of pre- and post-pubertal castration on bone weight and measurements has been studied in 3 groups of Piemontese male cattle (EC - early castrated, LC - late castrated, IM - intact reared in the same environmental conditions and slaughtered at about 18 month of age, at about 550 kg of l.w., and at the same commercial fattening degree. At side commercial dissection all separated bones were weighted, and on the main ones (scapula, humerus, radius, femur, and tibia linear measures were recorded and then some conformation ratios were calculated (weight/length, length/width, and length/circumference. Data were analysed by GLM ANCOVA procedure, correcting data on side weight to avoid bias due to differences in carcass weight. No differences were found in side bone weight (23.58 ± 2.61 kg, so as in single bone weight, measures and ratios.

  8. Castration-induced expression of caspase-1 in epithelia of accessory sex organs in male rats

    Institute of Scientific and Technical Information of China (English)

    Masao Izawa; Mitunori Kimura; Tomiko Yamada; Makoto Saji

    2001-01-01

    Aim: As an attempt to clarify the molecular basis of castration-induced apoptosis, this study was undertaken to demonstrate the expression of caspase-1 in male accessory sex organs of rats. Methods and results: cDNA of rat caspase-1 was cloned by reverse transcription-polymerase chain reaction from the ventral prostates. The open reading frame predicts 402 amino acids, which shows more than 91% and 63 % identity to those of mouse and human, respec tively. Northern analyses demonstrated the presence of castration-induced up-regulation of the 1.6 kb transcript in the ventral prostate and the seminal vesicles. Finally, the authors demonstrated the caspase-1 transcripts in the epithelia of these tissues by in situ hybridization analyses. Conclusion: Castration induces the expression of caspase-1 tran scripts in the epithelia of ventral prostate and seminal vesicle. These observations suggest a possible role of caspase-1 in apoptosis in male accessory sex organs.

  9. Current perspectives on the optimal age to spay/castrate dogs and cats

    Directory of Open Access Journals (Sweden)

    Howe LM

    2015-05-01

    Full Text Available Lisa M HoweDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USAAbstract: Spaying and castrating of dogs and cats has been considered for decades to be a routine standard of practice in veterinary medicine in the US for the prevention of numerous undesirable behaviors, medical conditions, and diseases. Additionally, the procedures have been promoted as a method of curbing the severe pet-overpopulation problem in the US. Recently, however, this routine practice has come under scrutiny and become a very controversial topic. The general wisdom and safety of the procedures have been questioned by those who are concerned that the procedures may have some unintended consequences that are only recently being recognized. The purpose of this paper is to critically examine the scientific literature regarding elective spay/castration procedures and present both risks and benefits of elective gonadectomy. After the literature is examined, it becomes clear that there may not be a single absolute optimal age to spay or castrate all dogs and cats, but that the optimal age may be dependent upon several factors, including species, breed, body size, and breed-specific diseases, among others. Determining the optimal age to perform elective gonadectomy is much clearer in cats, and the literature demonstrates that the procedures can typically be safely performed at any age after 6–8 weeks of age. The optimal age to spay or castrate dogs of certain breeds (rottweiler, golden retriever, Labrador retriever, and vizsla is becoming less clear as studies are being conducted as to the health benefits and risks in those breeds. This review will examine these controversies and make recommendations as to the optimal age to spay/castrate dogs based upon the scientific literature.Keywords: gonadectomy (neuter, ovariohysterectomy (spay, castration, neoplasia, longevity, orthopedic

  10. Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels.

    Science.gov (United States)

    Magari, Tomohiro; Shibata, Yasuhiro; Arai, Seiji; Kashiwagi, Bunzo; Suzuki, Keiji; Suzuki, Kazuhiro

    2014-01-01

    We examined the effect of androgens on bladder blood flow (BBF), bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group (control group), groups castrated at the age of 8 weeks (group 8wPC) and groups castrated at the age of 4 weeks (group 4wPC). Each rat was used at the age of 20 weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid (AA) solution. Maximum voiding pressure and voiding interval were measured. The bladder and iliac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened (P control group (Pcontrol group (Pblood vessels.

  11. Angiogenin mediates androgen-stimulated growth of prostate cancer cells and correlates with castration resistance

    OpenAIRE

    Li, Shuping; Hu, Miaofen G.; Sun, Yeqing; YOSHIOKA, NORIE; IBARAGI, SOICHIRO; Sheng, Jinghao; Sun, Guangjie; Kishimoto, Koji; Hu, Guo-fu

    2013-01-01

    Androgen receptor (AR) is a critical effector of prostate cancer (PCa) development and progression. Androgen-dependent PCa rely on the function of AR for growth and progression. Many castration-resistant PCa continue to depend on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of PCa cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the...

  12. Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Scott T Tagawa; Himisha Beltran

    2011-01-01

    In essentially just 1 year's time,we have seen science translated into exciting new therapeutic agents for men with metastatic castration-resistant prostate cancer (CRPC),1 most recently with the United States Food and Drug Administration (FDA) approval of abiraterone acetate in combination with prednisone.2 While prostate cancer has been known to be highly responsive to surgical or medical castration for well over half a century,3 what was once termed 'hormone refractory' prostate cancer inevitably developed,leading to cancerrelated death.Many consider the introduction of chemotherapy for CRPC initially for symptomatic benefit,then with improvements in survival,a substantial step forward.

  13. AB228. Research on the mechanism of androgen replacement therapy improving erectile dysfunction in castrated rats

    OpenAIRE

    Cui, Kai; Li, Rui; WANG, Tao; Zhang, Yan; Wang, Shaogang; Rao, Ke; Liu, Jihong

    2016-01-01

    Objective To investigate the mechanism of androgen replacement therapy (ART) improving erectile dysfunction (ED) in castrated rats. Methods We randomly divided 40 8-week-old healthy male SD rats into 4 groups: group A was the control, and rats of the group B, C and D were castrated, then rats in the groups C and D were treated with different concentrations of testosterone undecanoate orally every day (C: 10 mg/kg, D: 20 mg/kg), while other groups with 0.9% NS instead. 8weeks’ treatment later,...

  14. Effects of neonatal surgical castration or immunocastration on the adrenal axis of males pigs

    OpenAIRE

    PRUNIER, Armelle; Robic, Annie; Leclercq, Caroline; Feve, Katia; Merlot, Elodie

    2015-01-01

    To explore the effect of the suppression of testicular hormones on the adrenal axis, we compared entire pigs (E, n = 18), pigs castrated early in life (SC, surgical castration at 5-6 days of age, n = 14) and pigs submitted to immunocastration around puberty (IC, vaccination against Improvac® at 88 and 117 days of age, n = 16). ). Saliva samples were collected at 112 and 147 days of age at various times during the day (9:00, 11:00, 17:00, 23:00, 5:00 and 9:00). Blood samples were collected jus...

  15. Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs.

    NARCIS (Netherlands)

    Teske, E.; Naan, E.C.; Dijk, E.M. van; Garderen, E. van; Schalken, J.A.

    2002-01-01

    The present retrospective study investigated the frequency of prostate carcinoma (PCA) among prostate abnormalities in dogs and determined whether castration influences the incidence of PCA in dogs. During the years 1993-1998, 15363 male dogs were admitted to the Utrecht University Clinic of Compani

  16. Stilbenes inhibit androgen receptor expression in 22Rv1 castrate-resistant prostate cancer cells

    Science.gov (United States)

    Androgen receptor (AR) signaling plays an important role in the development and progression of prostate cancer (PCa). Importantly, AR continues to be expressed in advanced stages of castrate-resistant PCa (CRPC), where it can have ligand- independent activity. Identification of naturally occurring s...

  17. The first experience in using abiraterone acetate in patients with castration-refractory prostate cancer

    Directory of Open Access Journals (Sweden)

    L. M. Rapoport

    2015-01-01

    Full Text Available Even in the mid-twentieth century, Huggins and Hodges proved the susceptibility of prostate cancer cells to hormonal manipulations, by using surgical castration as an example. An average of 18–36 months after initiation of first-line hormonal therapy, patients develop the castration resistance in prostate cancer, one of the causes of which was hyperproduction of the tumor receptors of prostate cancer cells and their hypersusceptibility to the castration levels of testosterone. Long-term treatment in patients with castration-refractory prostate cancer was extremely symptomatic and quality of life and overall survival were low. In the 2000s, investigations aimed at designing drugs to treat this category of patients were underway, which have culminated in the advent of three drugs (two of which belong to chemotherapy that are now used in the Russian Federation. The second-line hormonal agent abiraterone acetate (Zytiga is one of these drugs, which was officially registered in 2011. Its mechanism of action is due to inhibition of the enzyme CYP17, leading to the blocked synthesis of testosterone at all levels, including at the intracrine level, and achieving testosterone levels below the postcastration ones. The paper reviews the literature regarding abiraterone acetate and the first experience in using second-line hormonal therapy in three patients.

  18. Anxiety: the importunate companion. Psychoanalytic theory of castration and separation anxieties and implications for clinical technique.

    Science.gov (United States)

    Davies, Rosemary

    2012-10-01

    In this article I consider the implications of our differing psychoanalytic theories of anxiety on clinical technique. Drawing on differentiations between the focus on separation or castration anxiety and the relative neglect of the latter in contemporary writing, I look in detail at two clinical examples of psychoanalysis in borderline young adults to exemplify the issue.(1).

  19. Effect of castration age on carcass traits and meat quality of Simmental bulls

    Directory of Open Access Journals (Sweden)

    I. Andrighetto

    2010-01-01

    Full Text Available Italian beef management is usually based on entire males, since they show better growth rate and higher lean yield carcasses. Despite consumer’s preferences require lean meat, producers have been induced to consider the positive effect of castration especially on meat organoleptic traits.

  20. A single-center experience with abiraterone as treatment for metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Thortzen, Anita; Thim, Stine; Røder, Martin Andreas;

    2016-01-01

    BACKGROUND: Continuous stimulation of the androgen receptor (AR) axis is a prerequisite for growth in castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) is a potent inhibitor of extracellular and intracellular androgen synthesis by inhibition of the CYP-17 enzyme system, which...

  1. Serum biomarkers of bone metabolism in castration resistant prostate cancer patients with skeletal metastases

    Science.gov (United States)

    Background. Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value ...

  2. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm;

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra...

  3. Erotic Imagery and Self-Castration in Transvestism/Transsexualism: A Case Report

    Science.gov (United States)

    van Kammen, Daniel P.; Money, John

    1977-01-01

    After nearly 30 years of marriage, a 51-year-old man castrated himself to fulfill a long-standing fantasy of being a girl. It led the patient to elect low-dose maintenance on androgen to permit some degree of continued marital sex. The rehabilitative program as a transvestite man has continued for three years. (Author)

  4. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske;

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the fina...

  5. Mechanisms of acquired resistance to androgen receptor targeting drugs in castration resistant prostate cancer

    OpenAIRE

    Chism, David D.; De Silva, Dinuka; Whang, Young E.

    2014-01-01

    After initial response to androgen receptor targeting drugs abiraterone or enzalutamide, most patients develop progressive disease and therefore, castration resistant prostate cancer (CRPC) remains a terminal disease. Multiple mechanisms underlying acquired resistance have been postulated. Intratumoral androgen synthesis may resume after abiraterone treatment. A point mutation in the ligand binding domain of androgen receptor may confer resistance to enzalutamide. Emergence of androgen recept...

  6. An evaluation of stress responses, simplicity and cost of pinhole castration as an alternative technique for male dog sterilization

    Directory of Open Access Journals (Sweden)

    J. Okwee-Acai,

    2012-01-01

    Full Text Available Pinhole castration is a novel minimally invasive procedure for calf or kid castration. We evaluated stress, simplicity and costs of the technique in mongrel puppies (N=15. The puppies were divided into three groups: control i.e. not treated; second surgical castration and third pinhole castration. Stress was monitored by daily recording of rectal temperatures and assay of plasma cortisol concentration. Testicular histopathology was used to evaluate effectiveness of the method. Material requirements, costs and length of pinhole or surgical castration cases were compared. Surgery provoked higher febrile and cortisol responses than pinhole castration, however, the responses took longer to resolve in the pinhole treated animals. Each pinhole procedure required: xylazine 2% (0.2ml, syringe, needle and suture (10cm. Surgery meanwhile, required: xylazine 2% (0.2ml, 2 syringes, suture (15cm, razor, surgical blade, antibiotics, antiseptics, cotton and 1 ml ketamine (50mg/ml. Material cost for a surgery case was about thrice a pinhole case. Average time for pinhole was 14 minutes while surgery took about 35 minutes. We concluded that, compared to standard surgical castration, the pinhole technique is, less stressful, quicker, simpler and is a cheaper alternative for male dog sterilization. The technique should, therefore, be popularized in veterinary schools and practices for wider application.

  7. Evaluation of the anaesthetic depth during piglet castration under an automated isoflurane-anaesthesia at farm level.

    Science.gov (United States)

    Schwennen, Cornelia; Kolbaum, Nina; Waldmann, Karl-Heinz; Höltig, Doris

    2016-01-01

    Piglet castration under isoflurane-anaesthesia could represent an alternative to the practice of castration without anaesthesia. The objective of this study was to evaluate practicality and effectiveness of an automated isoflurane-anaesthesia for castration. A field study on three different farms in Germany (farm A, B: 200 sows; C: 540 sows) was performed. In total, 1429 (1166 anaesthetised and 263 conventionally castrated) male piglets (age: 1-8 days; bodyweight: 0.7-3.7 kg) were monitored. All piglets were treated with nonsteroidal anti-inflammatory drugs directly before castration. Castration and anaesthesia were performed by the farm-manager in presence of a veterinarian. All farmers used the PIGNAP Pro® (Agrosystems GmbH, CH) anaesthetic device (5 vol.% isoflurane, 30% oxygen; flow rate: 2 l/min). Vocalisation and defensive movements of 1166 anaesthetised piglets was rated using a scoring system. Presence or absence of the palpebral- and flexor-reflex was noted. Approximately every second piglet was weighed and oxygen-saturation and pulse- frequency of 231 animals were measured during treatment. Rectal temperatures before and after castration of 264 anaesthetised and 263 conventionally castrated piglets were compared. Only 77% of the anaesthetised piglets showed a sufficient anaesthetic depth based on the assessment of reflexes as well as vocalisations and defensive movements. It was found that the probability for a sufficient depth of anaesthesia decreases with increasing age and weight. The measurements of the pulse-frequency and oxygen-saturation showed an average oxygen-saturation of 98% and an average heart rate of 270/min during anaesthesia. The conventionally castrated piglets had significantly higher rectal temperatures in comparison to the anaesthetised (p piglets is not adequate for commercial application of this technology.

  8. Evaluation of the anaesthetic depth during piglet castration under an automated isoflurane-anaesthesia at farm level.

    Science.gov (United States)

    Schwennen, Cornelia; Kolbaum, Nina; Waldmann, Karl-Heinz; Höltig, Doris

    2016-01-01

    Piglet castration under isoflurane-anaesthesia could represent an alternative to the practice of castration without anaesthesia. The objective of this study was to evaluate practicality and effectiveness of an automated isoflurane-anaesthesia for castration. A field study on three different farms in Germany (farm A, B: 200 sows; C: 540 sows) was performed. In total, 1429 (1166 anaesthetised and 263 conventionally castrated) male piglets (age: 1-8 days; bodyweight: 0.7-3.7 kg) were monitored. All piglets were treated with nonsteroidal anti-inflammatory drugs directly before castration. Castration and anaesthesia were performed by the farm-manager in presence of a veterinarian. All farmers used the PIGNAP Pro® (Agrosystems GmbH, CH) anaesthetic device (5 vol.% isoflurane, 30% oxygen; flow rate: 2 l/min). Vocalisation and defensive movements of 1166 anaesthetised piglets was rated using a scoring system. Presence or absence of the palpebral- and flexor-reflex was noted. Approximately every second piglet was weighed and oxygen-saturation and pulse- frequency of 231 animals were measured during treatment. Rectal temperatures before and after castration of 264 anaesthetised and 263 conventionally castrated piglets were compared. Only 77% of the anaesthetised piglets showed a sufficient anaesthetic depth based on the assessment of reflexes as well as vocalisations and defensive movements. It was found that the probability for a sufficient depth of anaesthesia decreases with increasing age and weight. The measurements of the pulse-frequency and oxygen-saturation showed an average oxygen-saturation of 98% and an average heart rate of 270/min during anaesthesia. The conventionally castrated piglets had significantly higher rectal temperatures in comparison to the anaesthetised (p < 0.0001). The result of 77% sufficiently anaesthetised piglets is not adequate for commercial application of this technology. PMID:26904895

  9. Effects of castration and testosterone replacement on veno-occlusion during penile erection in the rat

    Institute of Scientific and Technical Information of China (English)

    Yu-TianDAI; VivienneStopper; RonaldLewis; ThomasMills

    1999-01-01

    Aim: To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penile strutures which control outflow. Methods: Using CASTRATE and TESTO rots, measurement was made of mean arterial pressure (MAP), intracavemosal pressure (CCP), and intracavemosal flow (CCF) during erection resulting from stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusion into the cavemosal sinuses before and after treatment with sodium nitropmsside (SNP, a nitric oxide donor drug) to fully relax cavemosal smooth muscle. Penile tissue was also collected to measure the content of a actin and proliue and hydroxyproline to determine if brief withdrawal of androgenic support led to changes in the number of smooth muscle cells or the collagen content of the tissue. Resttlts: Infusion of saline into the cavemosal sinuses demonstrated that veno-occlusion was defective in CASTRATE rats while veno-occlusion was fully functional in TESTO animals.Funtmmore, veno-occlusion could be induced in CASTRATE rats if they were first neared with SNP. This observation suggests that failure of veno-occlusion in the CASTRATE rats is due to a deficiency in the production of NO resulting in a reduction in the degree of relaxation of the penile smooth muscle. The measurements of smooth muscle a a ctin and proline and hydroxyproline content of collagen showed that both were unaffected by castration and that the basic structure of the penis did not degenerate after one week without androgenic support. Conclusion: Thesere sults can be inteipreted to mean that androgens control the veno-occlusive mechanism indirectly via a NO dependent mechanism and not by maintaining the structures of the penis which are essential to veno-ocelusion. ( Asian J Androl 1999 Jun; 1: 53-59)

  10. Performance of intact and castrated beef cattle in an intensive croppasture rotation system

    Directory of Open Access Journals (Sweden)

    Tercilio Turini

    2015-07-01

    Full Text Available This research had as objective to evaluate the performance of intact or castrated beef cattle in a croppasture rotation system. The experiment was conducted during 2004 and 2005, and carried out at the Cooperativa Agropecuária Mourãoense (COAMO Experimental Farm, in Campo Mourão city, Paraná state. It was used a completely randomized design, with two treatments, intact or castrated. Forty ½Angus+½Nelore crossbred animals, with average age of nine months, were used. Half of the animals were castrated at weaning, and the other half was kept intact. Pasture was composed of two areas. The winter field, established after soybean crop, was composed by a mixture of black oat (Avena strigosa and Italian ryegrass (Lolium multiforum. The summer field was composed by stargrass (Cynodon nlemfuensis and Mombaça grass (Panicum maximum. During the winter time it was used a continues grazing system, with regulator animals (put and take, and during the summer an intensive rotational system, with regulator animals and fixed grazing period. Intact animals presented higher average daily weight gain (0.907 vs 0.698 kg, slaughter weight (490.9 vs 442.2 kg, and hot carcass weight (250.2 vs 232.6 kg. Slaughter age was influenced by sexual condition, being lesser in the intact animals. Carcass dressing percentage was similar for the groups. Castrated animals showed better finishing fat cover and backfat thickness (3.45 vs 2.70 mm compared to intact ones. Therefore, it can be concluded that intact animals presents better performance than castrated ones when finished in an intensive crop-pasture rotation system, however, they may not present the minimum required fat cover, when slaughter at young ages.

  11. Labour time required for piglet castration with isoflurane-anaesthesia using shared and stationary inhaler devices.

    Science.gov (United States)

    Weber, Sabrina; Das, Gürbüz; Waldmann, Karl-Heinz; Gauly, Matthias

    2014-01-01

    Isoflurane-anaesthesia combined with an analgesic represents a welfare-friendly method of pain mitigation for castration of piglets. However, it requires an inhaler device, which is uneconomic for small farms. Sharing a device among farms may be an economical option if the shared use does not increase labour time and the resulting costs. This study aimed to investigate the amount and components of labour time required for piglet castration with isoflurane anaesthesia performed with stationary and shared devices. Piglets (N = 1579) were anaesthetised with isoflurane (using either stationary or shared devices) and castrated.The stationary devices were used in a group (n = 5) of larger farms (84 sows/farm on an average), whereas smaller farms (n = 7; 32 sows/farm on an average) shared one device. Each farm was visited four times and labour time for each process-step was recorded. The complete process included machine set-up, anaesthesia and castration by a practitioner, and preparation, collection and transport of piglets by a farmer. Labour time of the complete process was increased (P = 0.012) on farms sharing a device (266 s/piglet) compared to farms using stationary devices (177 s/ piglet), due to increased time for preparation (P = 0.055), castration (P = 0.026) and packing (P = 0.010) when sharing a device. However, components of the time budget of farms using stationary or shared devices did not differ significantly (P > 0.05). Cost arising from time spent by farmers did not differ considerably between the use of stationary (0.28 Euro per piglet) and shared (0.26 Euro) devices. It is concluded that costs arising from the increased labour time due to sharing a device can be considered marginal, since the high expenses originating from purchasing an inhaler device are shared among several farms.

  12. Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. VI. Effects of short term castration

    DEFF Research Database (Denmark)

    Kjaer, K; Kirkeby, S; Blecher, S R

    1983-01-01

    The regional histology and esterase activity of the mouse epididymis after 24, 48, and 72 hr castration is reported. Differential sensitivity to androgen deprivation among the various epithelial cell types is described, allowing of positive identification of the cell types previously observed...... to survive long-term castration. The possibility of an androgen binding protein, as described in the rat and rabbit, is suggested on morphological grounds. The epididymal body appears to contain a class of highly androgen sensitive cells that degenerate rapidly following castration and a second class...

  13. Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-/lo castration-resistant cells.

    Science.gov (United States)

    Rycaj, Kiera; Cho, Eun Jeong; Liu, Xin; Chao, Hsueh-Ping; Liu, Bigang; Li, Qiuhui; Devkota, Ashwini K; Zhang, Dingxiao; Chen, Xin; Moore, John; Dalby, Kevin N; Tang, Dean G

    2016-03-22

    We have recently demonstrated that the undifferentiated PSA-/lo prostate cancer (PCa) cell population harbors self-renewing long-term tumor-propagating cells that are refractory to castration, thus representing a therapeutic target. Our goals here are, by using the same lineage-tracing reporter system, to track the dynamic changes of PSA-/lo and PSA+ cells upon castration in vitro, investigate the molecular changes accompanying persistent castration, and develop large numbers of PSA-/lo PCa cells for drug screening. To these ends, we treated LNCaP cells infected with the PSAP-GFP reporter with three regimens of castration, i.e., CDSS, CDSS plus bicalutamide, and MDV3100 continuously for up to ~21 months. We observed that in the first ~7 months, castration led to time-dependent increases in PSA-/lo cells, loss of AR and PSA expression, increased expression of cancer stem cell markers, and many other molecular changes. Meanwhile, castrated LNCaP cells became resistant to high concentrations of MDV3100, chemotherapeutic drugs, and other agents. However, targeted and medium-throughput library screening identified several kinase (e.g., IGF-1R, AKT, PI3K/mTOR, Syk, GSK3) inhibitors as well as the BCL2 inhibitor that could effectively sensitize the LNCaP-CRPC cells to killing. Of interest, LNCaP cells castrated for >7 months showed evidence of cyclic changes in AR and the mTOR/AKT signaling pathways potentially involving epigenetic mechanisms. These observations indicate that castration elicits numerous molecular changes and leads to enrichment of PSA-/lo PCa cells. The ability to generate large numbers of PSA-/lo PCa cells should allow future high-throughput screening to identify novel therapeutics that specifically target this population. PMID:26871947

  14. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    Science.gov (United States)

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  15. Resource efficiency and economic implications of alternatives to surgical castration without anaesthesia.

    Science.gov (United States)

    de Roest, K; Montanari, C; Fowler, T; Baltussen, W

    2009-11-01

    This paper presents an analysis of the economic implications of alternative methods to surgical castration without anaesthesia. Detailed research results on the economic implications of four different alternatives are reported: castration with local anaesthesia, castration with general anaesthesia, immunocastration and raising entire males. The first three alternatives have been assessed for their impact on pig production costs in the most important pig-producing Member States of the EU. The findings on castration with anaesthesia show that cost differences among farms increase if the anaesthesia cannot be administered by farmers and when the veterinarian has to be called to perform it. The cost of veterinarian service largely affects the total average costs, making this solution economically less feasible in small-scale pig farms. In all other farms, the impact on production costs of local anaesthesia is however limited and does not exceed 1 €ct per kg. General anaesthesia administered by inhalation or injection of Ketamin in combination with a sedative (Azaperone, Midazolan) is more expensive. These costs depend heavily on farm size, as the inhalation equipment has to be depreciated on the largest number of pigs possible. The overall costs of immunocastration - including the cost of the work load for the farmer - has to be evaluated against the potential benefits derived from higher daily weight gain and feed efficiency in comparison with surgical castrates. The economic feasibility of this practice will finally depend on the price of the vaccine and on consumer acceptance of immunocastration. The improvement in feed efficiency may compensate almost entirely for the cost of vaccination. The main advantages linked to raising entire males are due to the higher efficiency of feed conversion, to the better growth rate and to the higher leanness of carcass. A higher risk of boar taint on the slaughter line has to be accounted for. Raising entire males should not

  16. Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

    OpenAIRE

    Decker, Keith F.; Zheng, Dali; He, Yuhong; Bowman, Tamara; Edwards, John R.; Jia, Li

    2012-01-01

    The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant ...

  17. Protein profiles in various epididymal segments of normal and castrated rats

    Institute of Scientific and Technical Information of China (English)

    PremenduP.Mathur; AileenMarshall; C.Y.Cheng

    2000-01-01

    Aim: Epididymal proteins are known to play an important role in the maturation of spermatozoa. We ought to determine if there are regional differences in androgen-dependent epididymal proteins. Methods: A group of adult rats was castrated and epididymides were removed three days following castration. The epididymides were dissected into caput,corpus and cauda segments, homogenized, and proteins were fractionated by anion exchange HPLC. Proteins in selected fractions were resolved by SDS-PAGE and visualized by silver staining. Results: It was observed that the levels of multiple proteins drastically reduced in the various regions of epididymis of the orchiectomized rats. Conclusion: The epididymal proteins appear to be useful markers to study androgenic action in the epididymis. ( Asian J Androl 2000 ;2: 57-64)

  18. How I do it: Prescribing abiraterone acetate for metastatic castration resistant prostate cancer.

    Science.gov (United States)

    Wang, Yuding; Dason, Shawn; Shayegan, Bobby

    2016-08-01

    Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17, a key enzyme in androgen biosynthesis. The efficacy and safety of AA in improving survival and quality of life in metastatic castration resistant prostate cancer (mCRPC) has been demonstrated in two landmark clinical trials (COU-AA-301 and COU-AA-302). This article will review the rationale, pharmacology, clinical indications and contraindications, administration, and adverse effects of AA administration in mCRPC. PMID:27544566

  19. Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Rosenberg JE

    2012-01-01

    Full Text Available Yasser Rehman1, Jonathan E Rosenberg21Division of Hospital Medicine, UMass Memorial Healthcare, Worcester, MA, USA; 2Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC, which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17. This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.Keywords: CRPC, abiraterone, CYP17, inhibitors, androgens, castration resistant prostate cancer

  20. Both Castration and Goserelin Acetate Ameliorate Myocardial Ischemia Reperfusion Injury and Apoptosis in Male Rats

    Science.gov (United States)

    Hadi, Najah R.; Yusif, Fadhil G.; Yousif, Maitham; Jaen, Karrar K.

    2014-01-01

    Although reperfusion of an ischemic organ is essential to prevent irreversible tissue damage, it may amplify tissue injury. This study investigates the role of endogenous testosterone in myocardial ischemia reperfusion and apoptosis in male rats. Material and method. Twenty four male rats were randomized into 4 equal groups: Group (1), sham group, rats underwent the same anesthetic and surgical procedure as the control group except for LAD ligation; Group (2), Active control group, rats underwent LAD ligation; Group (3), castrated, rats underwent surgical castration, left 3wks for recovery, and then underwent LAD ligation; and Group (4), Goserelin acetate treated, rats received 3.6 mg of Goserelin 3 wks before surgery and then underwent LAD ligation. At the end of experiment, plasma cTn I, cardiac TNF-α, IL1-β, ICAM-1, and Apoptosis level were measured and histological examination was made. Results. Compared to sham group, the levels of myocardial TNF-α, IL-1β, ICAM-1, apoptosis, and plasma cTn I were significantly increased (P < 0.05) in control group and all rats showed significant myocardial injury (P < 0.05). Castration and Goserelin acetates significantly counteract the increase in myocardial levels of TNF-α, IL-1β, ICAM-1, plasma cTn I, and apoptosis (P < 0.05) and significantly reduce (P < 0.05) the severity of myocardial injury. We conclude that castration and Goserelin acetates ameliorate myocardial I/R injury and apoptosis in rats via interfering with inflammatory reactions. PMID:24729888

  1. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer

    OpenAIRE

    Fizazi, Karim; Albiges, Laurence; Loriot, Yohann; Massard, Christophe

    2015-01-01

    Androgen deprivation therapy is the standard of care for patients with advanced hormone-sensitive prostate cancer. Despite an initial response, most patients progress to castration-resistant prostate cancer (CRPC). The realization that CRPC remains driven by androgen receptor (AR) signaling has formed the basis for a new generation of agents targeting the AR axis. Two of these agents, abiraterone acetate and enzalutamide, have been shown to prolong overall survival in patients with CRPC. Seve...

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

    OpenAIRE

    Mauro Silvani; Nicola Mondaini; Alessandro Zucchi

    2015-01-01

    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 liter...

  3. Predictors of Time to Metastasis in Castration-Resistant Prostate Cancer.

    OpenAIRE

    Moreira, DM; Howard, LE; Sourbeer, KN; Amarasekara, HS; Chow, LC; Cockrell, DC; Hanyok, BT; Aronson, WJ; Kane, CJ; Terris, MK; Amling, CL; Cooperberg, MR; Liede, A; Freedland, SJ

    2016-01-01

    To investigate predictors of time to metastasis among men treated with androgen deprivation therapy (ADT) for non-metastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.Retrospective analysis of 458 non-metastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time ze...

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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...

  6. Intratumoral steroidogenesis in castration-resistant prostate cancer: a target for therapy

    OpenAIRE

    Armandari, Inna; Hamid, Agus Rizal; Verhaegh, Gerald; Schalken, Jack

    2014-01-01

    Development of castration-resistant prostate cancer (CRPC) in a low androgen environment, arising from androgen deprivation therapy (ADT), is a major problem in patients with advanced prostate cancer (PCa). Several mechanisms have been hypothesized to explain the progression of PCa to CRPC during ADT, one of them is so called persistent intratumoral steroidogenesis. The existence of intratumoral steroidogenesis was hinted based on the residual levels of intraprostatic testosterone (T) and dih...

  7. Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer

    OpenAIRE

    Lindsay, C. R.; Le Moulec, S.; Billiot, F.; Loriot, Y; Ngo-Camus, M.; Vielh, P; Fizazi, K; Massard, C; Farace, F.

    2016-01-01

    Background High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRP...

  8. Starvation reveals the cause of infection-induced castration and gigantism.

    Science.gov (United States)

    Cressler, Clayton E; Nelson, William A; Day, Troy; McCauley, Edward

    2014-10-01

    Parasites often induce life-history changes in their hosts. In many cases, these infection-induced life-history changes are driven by changes in the pattern of energy allocation and utilization within the host. Because these processes will affect both host and parasite fitness, it can be challenging to determine who benefits from them. Determining the causes and consequences of infection-induced life-history changes requires the ability to experimentally manipulate life history and a framework for connecting life history to host and parasite fitness. Here, we combine a novel starvation manipulation with energy budget models to provide new insights into castration and gigantism in the Daphnia magna-Pasteuria ramosa host-parasite system. Our results show that starvation primarily affects investment in reproduction, and increasing starvation stress reduces gigantism and parasite fitness without affecting castration. These results are consistent with an energetic structure where the parasite uses growth energy as a resource. This finding gives us new understanding of the role of castration and gigantism in this system, and how life-history variation will affect infection outcome and epidemiological dynamics. The approach of combining targeted life-history manipulations with energy budget models can be adapted to understand life-history changes in other disease systems.

  9. 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.

  10. Effect of castration age on weight and size of some muscles in Piemontese male cattle

    Directory of Open Access Journals (Sweden)

    D. Biagini

    2010-04-01

    Full Text Available Effect of pre- and post-pubertal castration on muscle weight and measurements has been studied in 3 groups of Piemontese male cattle (EC - early castrated, LC - late castrated, IM - intact reared in the same environmental conditions and slaughtered at about 18 month of age, at about 550 kg of l.w., and at the same commercial fattening degree. At side commercial dissection all separated muscles or meat cuts were weighted, and on the most regular ones (regular roll, shoulder clod – “copertina”, blade filet, strip loin, tenderloin, and eye round linear measures were recorded and then some conformation ratios (weight/length, length/width, and length/circumference were calculated. Data were analysed by GLM ANCOVA procedure, correcting data on side weight to avoid bias due to differences in carcass weight. Differences were found in meat weight, heavier in IM than in LC and EC (P<0.05, and fat weight, heavier in LC and EC than IM (P<0.01. Only the blade filet weight/length and length/circumference ratios were higher in EC than LC and IM (P<0.05 and in IM than EC (P<0.05 respectively, showing the poor effect of sexual neutralisation on weight and size of the considered muscles.

  11. Effect of tasting and information on consumer opinion about pig castration.

    Science.gov (United States)

    Kallas, Zein; Gil, José Maria; Panella-Riera, Nuria; Blanch, Marta; Font-i-Furnols, Maria; Chevillon, Patrick; De Roest, Kees; Tacken, Gemma; Oliver, Maria Angels

    2013-10-01

    Our research explored the relative importance of pig castration amongst other aspects of animal welfare, and the potential impact of information and sensory experiences on European Union (EU) consumers' preferences. The EU is considering a future ban on surgical pig castration by 2018 which may affect markets and consumers' preferences. We carried out an empirical study using consumer-level data obtained from questionnaires completed in a controlled environment by a total of 825 consumers. The experiment was carried out in six EU countries (Spain, United Kingdom, The Netherlands, France, Italy and Germany) which account for 66.0% of the EU-27's and 76.3% of the EU-15's meat production. Results show that consumers do not perceive pig castration to be a relevant aspect of animal welfare nor its relationship with meat quality. Consumers with healthy life styles, concerned about animal welfare and who have had a negative sensory experience with boar meat are willing to accept paying more to avoid boar taint. PMID:23747618

  12. Comparison of Intramuscular or Subcutaneous Injections vs. Castration in Pigs—Impacts on Behavior and Welfare

    Directory of Open Access Journals (Sweden)

    John McGlone

    2016-08-01

    Full Text Available Physical castration (PC is painful and stressful for nursing piglets. One alternative to PC is immunological castration (IC, but the pain and stress of handling associated with injections have not been assessed. The objectives of this study were to measure the pain and distress of subcutaneous (SQ and intramuscular (IM injections compared to PC in piglets, and to compare SQ or IM injections in finishing pigs. After farrowing, 3 to 5 d old male piglets were randomly assigned to (control no handling treatment (NO, sham-handling (SHAM, IM, SQ, or PC. Finishing pigs were assigned to NO, SHAM, IM, or SQ. Behavior was monitored for 1 h prior and 1 h post treatment in each age group. Social, feeding behaviors, and signs of pain were recorded. Finishing pigs treated with SQ injections had higher feeding behaviors pre-treatment than they did post-treatment. Overall, physical castrations caused measurable pain-like behaviors and general behavioral dysregulation at a much higher level than the other treatment groups. SQ and IM injections did not cause either significant behavioral or physiological alterations in piglets. SQ injections caused a decrease in finishing pig feed behaviors post treatment ( p = 0.02 and SHAM treated finishing pigs spent significantly more time lying than the other treatment groups. In general IM and SQ injections did not cause any other significant changes in behavior or physiology.

  13. Integrative Molecular Profiling Reveals Asparagine Synthetase Is a Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Cogdell, David; Dhillon, Jasreman; Tzelepi, Vassiliki; Efstathiou, Eleni; Koumakpayi, Ismaël H.; Saad, Fred; Luo, Dijun; Bismar, Tarek A.; Aparicio, Ana; Troncoso, Patricia; Navone, Nora; Zhang, Wei

    2013-01-01

    The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells. PMID:22245216

  14. Starvation reveals the cause of infection-induced castration and gigantism.

    Science.gov (United States)

    Cressler, Clayton E; Nelson, William A; Day, Troy; McCauley, Edward

    2014-10-01

    Parasites often induce life-history changes in their hosts. In many cases, these infection-induced life-history changes are driven by changes in the pattern of energy allocation and utilization within the host. Because these processes will affect both host and parasite fitness, it can be challenging to determine who benefits from them. Determining the causes and consequences of infection-induced life-history changes requires the ability to experimentally manipulate life history and a framework for connecting life history to host and parasite fitness. Here, we combine a novel starvation manipulation with energy budget models to provide new insights into castration and gigantism in the Daphnia magna-Pasteuria ramosa host-parasite system. Our results show that starvation primarily affects investment in reproduction, and increasing starvation stress reduces gigantism and parasite fitness without affecting castration. These results are consistent with an energetic structure where the parasite uses growth energy as a resource. This finding gives us new understanding of the role of castration and gigantism in this system, and how life-history variation will affect infection outcome and epidemiological dynamics. The approach of combining targeted life-history manipulations with energy budget models can be adapted to understand life-history changes in other disease systems. PMID:25143034

  15. Tissue fatty acid composition and estimated ∆ desaturase activity after castration in chicken broilers fed with linseed or sunflower oil.

    Science.gov (United States)

    Mašek, T; Starčević, K; Filipović, N; Stojević, Z; Brozić, D; Gottstein, Z; Severin, K

    2014-04-01

    The aims of this study were to investigate the influence of the short-term addition of sunflower and linseed oil and castration on fatty acid composition and desaturation indexes in chicken broilers. Forty-eight male Ross 308 chicken broilers were supplemented with 5% of sunflower or linseed oil. The four experimental groups were linseed oil supplementation and castration (LC), linseed oil without castration (LN), sunflower oil and castration (SC) and sunflower oil without castration (SN). There was no significant influence of castration or oil supplement on live weights, weight gain, feed intake or feed conversion. Castration resulted in an increase in polyunsaturated fatty acids (PUFA), total n3, n6, measured desaturation indexes and a decrease in the saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) content of abdominal fat. In breast muscle, castration increased PUFA and 18:3n3 values, while in the liver tissue, castration did not influence the parameters measured. Linseed oil supplementation significantly increased 18:3n3, n3 long chain polyunsaturated fatty acids (LC PUFA), total n3 and decreased total n6, n6/n3 ratio, and 20:4n6 content. Values for 20:4n6 were the highest in SC and the lowest in the LC group. Linseed oil also significantly decreased ∆5 and ∆4 desaturation indexes in the thighs and ∆5 and ∆5, 6 in abdominal fat and the liver. These results suggest that short-term supplementation of basal diet with 5% of linseed oil could significantly increase n3 LC PUFA and decrease n6/n3 ratio content in the edible tissues of chicken broilers, without adverse effects on growth performance. Meanwhile, castration only improved fatty acid profile in abdominal fat, which is not nutritionally important. The interactions observed between basal diet, supplemented oil, sex hormones and other non-nutritional factors must be elucidated in future trials in order to correctly predict the nutritional value of linseed-fed poultry.

  16. Abiraterone in the treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Mostaghel EA

    2014-01-01

    Full Text Available Elahe A Mostaghel Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC. Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an

  17. AB228. Research on the mechanism of androgen replacement therapy improving erectile dysfunction in castrated rats

    Science.gov (United States)

    Cui, Kai; Li, Rui; Wang, Tao; Zhang, Yan; Wang, Shaogang; Rao, Ke; Liu, Jihong

    2016-01-01

    Objective To investigate the mechanism of androgen replacement therapy (ART) improving erectile dysfunction (ED) in castrated rats. Methods We randomly divided 40 8-week-old healthy male SD rats into 4 groups: group A was the control, and rats of the group B, C and D were castrated, then rats in the groups C and D were treated with different concentrations of testosterone undecanoate orally every day (C: 10 mg/kg, D: 20 mg/kg), while other groups with 0.9% NS instead. 8weeks’ treatment later, we determined the level of serum testosterone and assessed the erectile function of rats. Western blot, immunohistochemistry were performed to detect the level of target proteins. Results (I) The level of serum testosterone and erectile function (Max ICP/MAP): group Bwas significantly lower than group A, C and D, and group D was higher compared with group C; (II) effect of castration and ART on endothelial cells and androgen receptor (AR)/vascular endothelial growth factor (VEGF)/cyclin A pathway: the expression of CD31, vWF and AR/VEGF/cyclin A in group B were lower than group A, C and D, and group D was higher compared with group C; (III) effect of castration and ART on corpus cavernosum smooth muscle cells (CCSMCs) and TGF-β/S1P2/RhoA/ROCK pathway: the expression of α-sma in group B were lower than group A, C and D, and group D was higher compared with group C; while the expression of TGF-β/S1P2/RhoA/ROCK1 were higher in group B than group A, C and D, and group D was lower compared with group C. Conclusions ART can improve ED in castrated rats through promoting the proliferation of corpus cavernosum endothelial cells by activating AR/VEGF/cyclin A pathway; decreasing the contraction of CCSMCs and corporal fibrosis by inhibiting TGF-β/S1P2/RhoA/ROCK pathway, which provides reference for revealing the mechanism of ART treating ED associated late-onset hypogonadism.

  18. Changes in gene expression following androgen receptor blockade is not equivalent to androgen ablation by castration in the rat ventral prostate

    Indian Academy of Sciences (India)

    Anil M Limaye; Irfan Asangani; Thyagarajan Kalyani; Paturu Kondaiah

    2008-06-01

    Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well-documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate, it is not clear whether all the gene expression changes post-castration are due to androgen depletion alone. To obtain insights into this, we performed differential display reverse transcriptase polymerase chain reaction (DD-RT-PCR) which resulted in the identification of castration and/or flutamide-regulated genes in the rat ventral prostate. These include clusterin, methionine adenosyl transferase II, and prostate-specific transcripts such as PBPC1BS, S100RVP and A7. While clusterin, PBPC1BS and methionine adenosyl transferase II are regulated by both castration and flutamide, S100 RVP and A7 are regulated by castration alone. Interestingly, we show that flutamide, unlike castration, does not induce apoptosis in the rat ventral prostate epithelium, which could be an underlying cause for the differential effects of castration and flutamide treatment. We propose that castration leads to enrichment and depletion of stromal and epithelial cell types, respectively, resulting in erroneous conclusions on some of the cell type-specific transcripts as being androgen regulated.

  19. Effect of a topical anaesthetic formulation on the cortisol response to surgical castration of unweaned beef calves.

    Science.gov (United States)

    McCarthy, D; Lomax, S; Windsor, P A; White, P J

    2016-01-01

    Impracticality and cost of existing pain management strategies during surgical castration of beef cattle have limited their widespread implementation on-farm. A farmer-applied topical anaesthetic formulation, originally developed and used commercially to mitigate the pain of mulesing in lambs, was investigated for its potential use for managing pain in surgically castrated calves. This formulation contained lidocaine, bupivacaine, adrenalin and cetrimide. In this study, 24 Angus bull calves were randomly allocated to (1) surgical castration (C, n=8), (2) surgical castration with the post-operative application of topical anaesthetic (CTA, n=8) and (3) sham castration/control (CON, n=8). The experiment was conducted over 2 days, with treatment groups evenly represented across each day. Calves were habituated to handling before the experiment and blood samples were collected for plasma cortisol measurement at defined time periods before, at and post treatment, (at -0.5, 0 h, then +0.5, 1, 1.5, 2, 4 and 6 h). There was a significant effect of time on cortisol concentrations across all treatment groups (Pcortisol response at 0 h. The effect of treatment was not significant (P=0.077), however, there was a trend for CON calves to display lower cortisol concentrations than C and CTA calves and CTA calves to display lower cortisol concentrations than C calves. The mean area under the curve (AUC) of CON calves was significantly lower than those of C and CTA calves (P=0.04), however, there was no significant difference between the AUCs of CTA and C calves. Immediate application of topical anaesthetic after surgical castration did not significantly reduce plasma cortisol concentrations. However, the trend for CTA calves to display lower cortisol concentrations than C calves warrants further investigation into the use of TA for pain relief of surgically castrated beef calves.

  20. Plasma cortisol and white blood cell responses in different breeds of bulls: a comparison of two methods of castration.

    Science.gov (United States)

    Chase, C C; Larsen, R E; Randel, R D; Hammond, A C; Adams, E L

    1995-04-01

    To determine plasma cortisol and white blood cell response to castration, Angus (n = 12, 21.4 mo of age), Hereford (n = 6, 21.2 mo of age), and Brahman (n = 24, 20.3 mo of age) bulls nearing maturity were either left intact as uncastrated controls (CON), surgically castrated (SUR) after lidocaine, or castrated by latex rubber banding (BAN). Before and through 35 d after castration (castration = d 0), animals were weighed and blood samples were collected for analysis of cortisol and total white blood cell (WBC) count at 2-, 3-, or 7-d intervals. There was a treatment x breed interaction for ADG from d 0 to 7 (P < .05). From d 0 to 14, 0 to 21, 0 to 28, and 0 to 35, ADG tended to be lower for SUR and BAN animals than for CON animals (castrated vs CON, P < or = .13). No significant differences in ADG were observed between SUR and BAN animals during these times. On d 0, from just before treatment to just after treatment, plasma cortisol concentration increased 3.2 ng/mL for SUR and .1 ng/mL for BAN (SEM = +/- .5 ng/mL; SUR vs BAN, P < .03). From d 0 pretreatment to d 2 after treatment, plasma cortisol concentration increased 1.5 ng/mL for castrated (SUR = 2.0 and BAN = 1.1 ng/mL) and decreased 1.6 ng/mL for CON (SEM = +/- .7 ng/mL; P < .04). Plasma cortisol concentration was negatively correlated (P < .001) with BW (r = -.17) and BW change (r = -.19).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7628975

  1. Effects of icariin on erectile function and expression of nitric oxide synthase isoforms in castrated rats

    Institute of Scientific and Technical Information of China (English)

    Wu-Jiang Liu; Zhong-Cheng Xin; Hua Xin; Yi-Ming Yuan; Long Tian; Ying-Lu Guo

    2005-01-01

    Aim: To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase (NOS)isoforms in castrated rats. Methods: Thirty-two adult male Wistar rats were randomly divided into one sham-operated group (A) and three castrated groups (B, C and D). One week after surgery, rats were treated with normal week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure (ICP)during electrostimulation of the cavernosal nerve. The serum testosterone (ST) levels, the percent of smooth muscle (PSM) in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase (nNOS),inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and phosphodiesterase V (PDE5) in corpus cavernosum (CC) were also evaluated. Results: ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A (P < 0.01). However, ICP, PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B (P < 0.05).Changes in ST and the expression of eNOS and PDE5 were not significant (P > 0.05) in groups C and D compared with those in group B. Conclusion: Oral treatment with icariin (> 98.6 % purity) for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.

  2. Possible mechanism of benign prostatic hyperplasia induced by androgen-estrogen ratios in castrated rats

    Directory of Open Access Journals (Sweden)

    Xiang-Yun Liu

    2010-01-01

    Full Text Available Objectives : To explore the role of androgen-estrogen balance in benign prostatic hyperplasia (BPH induced by varying doses of estradiol/testosterone propionate (E 2 /TP in castrated rats. Materials and Methods : A total of 222 rats were divided into 37 groups at random, including 35 groups of different E 2 /TP, one control, and one castrated group. All 37 groups except the control group were castrated, for eliminating endogenesis of testosterone in rats. The treated groups were administered testosterone propionate (TP; at the dosages of 0.15, 0.74, 3.7, 18.5, and 92.6 mg/kg, combined with estradiol (E 2 ; at the dosage of 0, 0.4, 2, 10, 50, 250, and 1250 μg/kg diluted in vegetable oil for 30 days, respectively, whereas the control groups received only vegetable oil. All prostate specimens were removed under anesthesia, then fixed and embedded in paraffin, for measuring the organ quotient, volume, area of prostate glandular cavity, and the height of prostate epithelia. Results : When the dosages of TP were 0.15, 3.7, 18.5, and 92.6 mg/kg, the degree of prostatic hyperplasia had no obvious dose-effect relationship with E 2 . When TP was 0.74 mg/kg, with the increase of the dosage of E 2 , the volume and quotient of prostate were increasing. However, when the dosage of E 2 exceeded 50 μg/kg, E 2 /TP was 5/74, the prostatic volume did not increase obviously. Conclusion : The proper levels of E2/TP play an important role in the pathogenesis of BPH. In rats, the balance point of E 2 /TP is 5/74.

  3. Opinion of the scientific panel on animal health and welfare on a request from the commission related to welfare aspects of the castration of piglets

    DEFF Research Database (Denmark)

    Gunn, Michael; Allen, Paul; Bonneau, Michel;

    2004-01-01

    Report - Annex to the Opinion of the Scientific Panel on Animal Health and Welfare on a request from the Commission related to welfare aspects of the castration of piglets......Report - Annex to the Opinion of the Scientific Panel on Animal Health and Welfare on a request from the Commission related to welfare aspects of the castration of piglets...

  4. Systemic treatment with epidermal growth factor but not insulin-like growth factor I decreases the involution of the prostate in castrated rats

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Sørensen, Flemming Brandt;

    2000-01-01

    Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrate...

  5. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  6. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  7. Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels

    Institute of Scientific and Technical Information of China (English)

    Tomohiro Magari; Yasuhiro Shibata; Seiji Arai; Bunzo Kashiwagi; Keiji Suzuki; Kazuhiro Suzuki

    2014-01-01

    We examined the effect of androgens on bladder blood lfow (BBF), bladder function and histological changes in castrated male rats. Male Wistar rats were classiifed into unoperated group (control group), groups castrated at the age of 8 weeks (group 8wPC) and groups castrated at the age of 4 weeks (group 4wPC). Each rat was used at the age of 20 weeks. BBF was measured using lfuorescent microspheres. Bladder cystometry was performed without anesthesia or restraint;the bladder was ifrst irrigated with saline and then with 0.25%acetic acid (AA) solution. Maximum voiding pressure and voiding interval were measured. The bladder and iliac artery were histologically examined for differences in smooth muscle and quantity of collagen ifber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened (P<0.001) following AA irrigation. No signiifcant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and iliac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group (P<0.01), while that at the iliac artery was decreased in group 4wPC compared to the control group (P<0.001). In conclusion, our ifndings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.

  8. Simultaneous Measurement of Serum Chemical Castration Agents and Testosterone Levels Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

    Science.gov (United States)

    Ko, Dae-Hyun; Lee, Kyunghoon; Jeon, Sun-Hee; Song, Sang Hoon; Yun, Yeo-Min; Chun, Sail; Kim, Hee Seung; Kim, Jin Young; In, Moon Kyo; Song, Junghan

    2016-05-01

    Chemical castration involves administration of drugs to prevent pathological sexual behavior, reduce abnormal sexual drive and treat hormone-dependent cancers. Various drugs have been used for chemical castration; however, substantial interindividual variability and side effects are often observed. In this study, we proposed a useful monitoring method for the application of chemical castration agents using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Testosterone, cyproterone acetate, medroxyprogesterone, goserelin acetate, leuprolide acetate and triptorelin acetate were analyzed by UPLC-MS-MS. The target drugs were extracted from serum samples by double protein precipitation using methanol. Testosterone-1,2-d2 and buserelin acetate were used as internal standards. Parameters of analytical performance were evaluated, including imprecision, linearity, ion suppression and detection capabilities. Testosterone measurements were compared with the results of immunoassays. Serum specimens from 51 subjects who underwent chemical castration were analyzed. All drugs and testosterone were well extracted and separated using our method. The method was essentially free from potential interferences and ion suppression. Within-run and between-run imprecision values were <15%. The lower limits of quantification were 0.125 and 0.5-1.0 ng/mL for testosterone and other drugs, respectively. Good correlations with pre-existing immunoassays for testosterone measurement were observed. Sera from subjects who underwent androgen deprivation therapy showed variable levels of drugs. We successfully developed a UPLC-MS-MS-based monitoring method for chemical castration. The performance of our method was generally acceptable. This method may provide a novel monitoring strategy for chemical castration to enhance expected effects while reducing unwanted side effects. PMID:26989223

  9. Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels

    Directory of Open Access Journals (Sweden)

    Tomohiro Magari

    2014-06-01

    Full Text Available We examined the effect of androgens on bladder blood flow (BBF, bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group (control group, groups castrated at the age of 8 weeks (group 8wPC and groups castrated at the age of 4 weeks (group 4wPC. Each rat was used at the age of 20 weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid (AA solution. Maximum voiding pressure and voiding interval were measured. The bladder and iliac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened (P < 0.001 following AA irrigation. No significant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and iliac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group (P< 0.01, while that at the iliac artery was decreased in group 4wPC compared to the control group (P< 0.001. In conclusion, our findings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.

  10. Dominant-negative androgen receptor inhibition of intracrine androgen-dependent growth of castration-recurrent prostate cancer.

    Directory of Open Access Journals (Sweden)

    Mark A Titus

    Full Text Available BACKGROUND: Prostate cancer (CaP is the second leading cause of cancer death in American men. Androgen deprivation therapy is initially effective in CaP treatment, but CaP recurs despite castrate levels of circulating androgen. Continued expression of the androgen receptor (AR and its ligands has been linked to castration-recurrent CaP growth. PRINCIPAL FINDING: In this report, the ligand-dependent dominant-negative ARΔ142-337 (ARΔTR was expressed in castration-recurrent CWR-R1 cell and tumor models to elucidate the role of AR signaling. Expression of ARΔTR decreased CWR-R1 tumor growth in the presence and absence of exogenous testosterone (T and improved survival in the presence of exogenous T. There was evidence for negative selection of ARΔTR transgene in T-treated mice. Mass spectrometry revealed castration-recurrent CaP dihydrotestosterone (DHT levels sufficient to activate AR and ARΔTR. In the absence of exogenous testosterone, CWR-R1-ARΔTR and control cells exhibited altered androgen profiles that implicated epithelial CaP cells as a source of intratumoral AR ligands. CONCLUSION: The study provides in vivo evidence that activation of AR signaling by intratumoral AR ligands is required for castration-recurrent CaP growth and that epithelial CaP cells produce sufficient active androgens for CaP recurrence during androgen deprivation therapy. Targeting intracrine T and DHT synthesis should provide a mechanism to inhibit AR and growth of castration-recurrent CaP.

  11. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer

    OpenAIRE

    Hussain, Maha; Carducci, Michael A.; Slovin, Susan; Cetnar, Jeremy; Qian, Jiang; McKeegan, Evelyn M.; Refici-Buhr, Marion; Chyla, Brenda; Shepherd, Stacie P.; Giranda, Vincent L.; Alumkal, Joshi J.

    2014-01-01

    Androgen receptor-mediated transcription is directly coupled with the induction of DNA damage, and castration-resistant tumor cells exhibit increased activity of poly (ADP-ribose) polymerase (PARP)-1, a DNA repair enzyme. This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and temozolomide (TMZ) in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot study. Patients with mCRPC ...

  12. Effect of castration timing and oral meloxicam administration on growth performance, inflammation, behavior, and carcass quality of beef calves.

    Science.gov (United States)

    Brown, A C; Powell, J G; Kegley, E B; Gadberry, M S; Reynolds, J L; Hughes, H D; Carroll, J A; Burdick Sanchez, N C; Thaxton, Y V; Backes, E A; Richeson, J T

    2015-05-01

    Beef bull calves (n = 62) were assigned randomly, within sire breed, to 1 of 4 treatments at birth. Treatments were 1) surgical castration near birth, 2) surgical castration near birth with oral administration of meloxicam (1 mg/kg BW), 3) surgical castration at weaning (WNG), or 4) surgical castration at weaning with oral administration of meloxicam (1 mg/kg BW; WMX). A subset of calves (n = 7/treatment group) were selected randomly near birth for blood collection, behavioral analyses, and rectal temperature (RT) records for a 7-d postcastration period on d 0 (birth), 1, 3, and 7, and on d 214 (weaning), 214 + 6 h, 215, 217, 221, and 228. Calf standing and lying activity were monitored from the same subsets by recording x- and y-axis positions of an accelerometer attached to the right metatarsus for 7 d postcastration. Calf BW was recorded throughout the entire production cycle, and carcass data were collected at slaughter. For statistical analyses, bulls left intact at birth were considered a positive control (BUL) for observations that occurred before their treatment application at weaning; likewise, bulls castrated at birth were considered a negative control (STR) during postweaning observations. No difference (P > 0.88) occurred in ADG between treatments throughout the preweaning period (d 0 to 214); however, 56-d postweaning ADG was greatest ( P= 0.02) in STR, intermediate in WMX, and least in WNG. At weaning, haptoglobin (Hp) was greater (P ≤ 0.005) for WNG and WMX compared to STR on d 214+6 h, 215, and 217, and Hp was greater (P = 0.05) in WNG compared to WMX on d 217. Neutrophils increased (P treatments. In this study, surgical castration at weaning, but not near birth, altered the acute phase response, behavior, and growth performance. Oral meloxicam reduced serum Hp and improved ADG briefly when administered to calves castrated at weaning. Oral administration of meloxicam may be efficacious for mitigating some of the stress and inflammation associated

  13. Effects of pain mitigation and method of castration on behavior and feedlot performance in cull beef bulls.

    Science.gov (United States)

    Repenning, P E; Ahola, J K; Callan, R J; Fox, J T; French, J T; Giles, R L; Peel, R K; Whittier, J C; Engle, T E

    2013-10-01

    The objectives of this study were to evaluate the effects of castration method (banding vs. surgical) and use of analgesia on behavior and feedlot performance in cull bulls. Angus, Hereford, and Angus-crossbred bulls (n = 20; initial BW = 384 ± 59.3 kg; 336 ± 20.1 d old) were housed in feedlot pens equipped with the ability to measure individual daily feed intake. A balanced randomized block design using a 2 × 2 factorial arrangement of treatments was used. A multimodal analgesia (MMA) protocol was used and consisted of sutcutaneous ketamine stun containing butorphanol (0.01 mg/kg BW), xylazine (0.02 mg/kg BW), ketamine (0.04 mg/kg BW), and a local 2% lidocaine hydrochloride anesthetic block of the spermatic cords (10 mL/cord) and scrotum (10 mL) on d 0. Flunixin meglumine (1.2 mg/kg) was administered intravenously on d 0, 1, 2, and 3 to MMA cattle. Cattle were stratified to treatments based on breed, BW, age, and a temperament score. Treatments included 1) band castration without analgesia (BND), 2) band castration with analgesia (BND-MMA), 3) surgical castration without analgesia (SURG), and 4) surgical castration with analgesia (SURG-MMA). All castrations were performed on d 0. Chute exit velocity (EV) and time in chute (TIC) were collected on d -9, 0, 1, 2, and 13. Willingness-to-enter-chute (WTE) score, rectal temperature (TEMP), heart rate (HR), and respiration (RESP) were collected on d 0, 1, 2, 3, and 13. Cattle were weighed on d -9 and 13 while feeding behaviors were collected continuously for 57 d precastration and 28 d postcastration. There was a tendency (P < 0.09) for ADG to be greater in cattle receiving analgesia. Both SURG treatments exhibited elevated TEMP on d 1 (P < 0.001) and 2 (P < 0.05) compared to BND treatments. Postcastration DMI was greater (P = 0.02) in MMA treatments compared with nonmedicated treatments throughout the trial. Meal duration was greater (P < 0.05) in BND than SURG castrates during the first week postcastration. Results

  14. Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic.

    Science.gov (United States)

    Imamura, Yusuke; Sadar, Marianne D

    2016-08-01

    The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer. PMID:27302572

  15. The effects of castration followed testosterone supplementation in prostatic complex of Artibeus planirostris (Chiroptera: Phyllostomidae).

    Science.gov (United States)

    Puga, Cíntia C I; Beguelini, Mateus R; Morielle-Versute, Eliana; Vilamaior, Patricia S L; Taboga, Sebastião R

    2016-06-01

    The prostatic complex (ventral and dorsal regions) of Artibeus planirostris exhibits seasonal variations throughout the year. Circulating testosterone was correlated with prostate weight, showing an increase from autumn to summer, with the highest peak in summer corresponding to the largest breeding season. This indicates that the level of serum testosterone influences variations in both testicular and prostatic weights. Serum testosterone levels seem to be closely related to the different responses of these glands throughout the year. The castration (consequent suppression of testosterone) and subsequent hormone supplementation may elucidate the relationship of these two glandular types with testosterone. Thus, the aim of this study was to evaluate the effect of castration and the testosterone supplementation in the male prostatic complex of A. planirostris. The results indicated that both prostatic regions were affected by the ablation of testosterone, presenting a decrease in cell proliferation and an increase in apoptosis. Similarly, the prostate was responsive to hormonal supplementation, having a recovery of the active morphophysiological pattern with testosterone supplementation. However, data have shown that the ventral region was more sensitive to changes in testosterone than the dorsal, presenting greater cell renewal. PMID:27032910

  16. Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

    Science.gov (United States)

    Caffo, Orazio; Lunardi, Andrea; Trentin, Chiara; Maines, Francesca; Veccia, Antonello; Galligioni, Enzo

    2016-01-01

    The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer. PMID:26721408

  17. Bilateral testicular self-castration due to cannabis abuse: a case report

    Directory of Open Access Journals (Sweden)

    Stuurman-Wieringa Roos E

    2011-08-01

    Full Text Available Abstract Introduction The self-mutilating patient is an unusual psychiatric presentation in the emergency room. Nonetheless, serious underlying psychiatric pathology and drug abuse are important background risk factors. A careful stepwise approach in the emergency room is essential, although the prognosis, follow-up, and eventual rehabilitation can be problematic. We present a unique and original case of bilateral self-castration caused by cannabis abuse. Case Presentation We report a case of a 40-year-old Berber man, who was presented to our emergency room with externalization of both testes using his long fingernails, associated with hemodynamic shock. After stabilization of his state, our patient was admitted to the operating room where hemostasis was achieved. Conclusion The clinical characteristics of self-mutilation are manifold and there is a lack of agreement about its etiology. The complex behavior associated with drug abuse may be one cause of self-mutilation. Dysfunction of the inhibitory brain circuitry caused by substance abuse could explain why this cannabis-addicted patient lost control and self-mutilated. To the best of our knowledge, this is the first case report which presents an association between self-castration and cannabis abuse.

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

    Directory of Open Access Journals (Sweden)

    Diane Ojo

    2015-11-01

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

  19. Spontaneous inflammatory pelvic disease in adult non-castrated female rats treated with estrogen

    Directory of Open Access Journals (Sweden)

    Aristóteles M G Ramos

    2005-02-01

    Full Text Available The adaptive immune response of the genital tract is under the control of sexual steroids; however, the influence of sex hormones on innate immune mechanisms of the genital mucosa are only beginning to be understood. We found that long-term estrogen treatment increases the risk for inflammatory pelvic diseases in adult non-castrated female rats. Female rats (110 g to 130 g received estrogen (10 rats; 17-beta estradiol, 50 mg pellet; 10 rats: subcutaneous weekly injection of estradiol valerate 0.166 mg/kg. Ten rats received a pellet of 17-beta estradiol and were treated with amoxicillin, 50 mg/kg after the 90th day of exposure to estrogen. Three control groups of ten rats were also used. The estrogen-treated rats developed an inflammatory pelvic disease, with abscess formation after the third month of hormonal treatment. All the surviving animals were killed after six months of hormonal exposure. Among 15 survivors of the two groups that received estrogen 13 animals presented tuboovarian abscesses. Among eight survivors of the group treated with amoxicillin, six had tuboovarian abscesses. None of the 30 control rats presented macro or microscopic signs of inflammatory disease in the uterus, tubes or ovaries. We conclude that estrogen impairs the defense mechanisms of the genital tract of non-castrated female rats, enhancing bacterial growth in the vagina and ascending infection to the uterus, tubes and ovaries.

  20. Cytotoxic chemotherapy in the contemporary management of metastatic castration-resistant prostate cancer (mCRPC).

    Science.gov (United States)

    Sonpavde, Guru; Wang, Christopher G; Galsky, Matthew D; Oh, William K; Armstrong, Andrew J

    2015-07-01

    For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long-term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration-sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies. PMID:25046451

  1. A comparison of slice characteristics and sensory characteristics of bacon from immunologically castrated barrows with bacon from physically castrated barrows, boars, and gilts.

    Science.gov (United States)

    Little, K L; Kyle, J M; Bohrer, B M; Schroeder, A L; Fedler, C A; Prusa, K J; Boler, D D

    2014-12-01

    The objectives were to compare slice characteristics and sensory attributes of bacon from immunologically castrated (IC) barrows with bacon from other sexes using a trained sensory panel. Bacon was obtained for sensory evaluation from 3 experiments. In Exp. 1, trimmed and squared bellies (n=180) of IC barrows, IC barrows fed ractopamine hydrochloride (IC+RAC), physically castrated (PC) barrows, intact males (IM), and gilts were used. Data were analyzed as a general linear mixed model and pen (n=48) served as the experimental unit. Treatment (sex or diet) was a fixed effect in all 3 experiments. In Exp. 2, untrimmed, natural fall bellies (n=96) from IC and PC barrows fed 0 or 30% or a withdrawal distillers dried grains with solubles (DDGS) program when slaughtered at 5 wk after the second dose (25 wk of age) were used. In Exp. 3, untrimmed, natural fall bellies (n=96) from IC and PC barrows fed the same experimental diets as in experiment 2 but slaughtered at 7 wk after the second dose (27 wk of age) were used. Data from Exp. 2 and 3 were analyzed as a 2×3 factorial arrangement in a randomized complete block design and pen was the experimental unit. Bellies from all 3 experiments were processed using the same protocols. In Exp. 1, IM had the greatest (Paroma and flavor scores among all treatments. No differences were detected among the other treatment groups for boar aroma or flavor. Intact males had the least (Paroma and flavor among all treatments. No differences were detected among the other treatment groups for bacon aroma or flavor. There were no differences in bacon aroma or off-flavor between IC and PC barrows slaughtered at 5 wk after the second dose regardless of DDGS feeding program. Bacon from PC barrows was saltier (Paroma, off-aroma, bacon flavor, or saltiness between IC and PC barrows slaughtered at 7 wk after the second dose regardless of DDGS feeding program. Total slice area of bacon slices from IC barrows slaughtered at 5 wk after the second dose

  2. Intratesticular and subcutaneous lidocaine alters the intraoperative haemodynamic responses and heart rate variability in male cats undergoing castration

    NARCIS (Netherlands)

    Moldal, E.R.; Eriksen, T.; Kirpensteijn, J.; Nødtvedt, A.; Kristensen, A.T.; Sparta, F.M.; Haga, H.A.

    2013-01-01

    Abstract OBJECTIVE: To evaluate the usefulness of intratesticular and subcutaneous lidocaine in alleviating the intraoperative nociceptive response to castration, measured by pulse rate (PR) and mean arterial pressure (MAP), and to test the applicability of heart rate variability (HRV) analysis in a

  3. HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer.

    Science.gov (United States)

    Ai, Junkui; Wang, Yujuan; Dar, Javid A; Liu, June; Liu, Lingqi; Nelson, Joel B; Wang, Zhou

    2009-12-01

    The development of castration-resistant prostate cancer (PCa) requires that under castration conditions, the androgen receptor (AR) remains active and thus nuclear. Heat shock protein 90 (Hsp90) plays a key role in androgen-induced and -independent nuclear localization and activation of AR. Histone deacetylase 6 (HDAC6) is implicated, but has not been proven, in regulating AR activity via modulating Hsp90 acetylation. Here, we report that knockdown of HDAC6 in C4-2 cells using short hairpin RNA impaired ligand-independent nuclear localization of endogenous AR and inhibited PSA expression and cell growth in the absence or presence of dihydrotestosterone (DHT). The dose-response curve of DHT-stimulated C4-2 colony formation was shifted by shHDAC6 such that approximately 10-fold higher concentration of DHT is required, indicating a requirement for HDAC6 in AR hypersensitivity. HDAC6 knockdown also inhibited C4-2 xenograft tumor establishment in castrated, but not in testes-intact, nude mice. Studies using HDAC6-deficient mouse embryonic fibroblasts cells showed that inhibition of AR nuclear localization by HDAC6 knockdown can be largely alleviated by expressing a deacetylation mimic Hsp90 mutant. Taken together, our studies suggest that HDAC6 regulates AR hypersensitivity and nuclear localization, mainly via modulating HSP90 acetylation. Targeting HDAC6 alone or in combination with other therapeutic approaches is a promising new strategy for prevention and/or treatment of castration-resistant PCa.

  4. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  5. Gender Differences in the Anatomy of the Perineal Glands in Guinea Pigs and the Effect of Castration

    DEFF Research Database (Denmark)

    Iburg, T. M.; Arnbjerg, J.; Ruelokke, M. L.

    2013-01-01

    Perineal glands in guinea pigs are part of the sebaceous glandular complex. Their secretions are used for scent marking. This is important for social status and can be seen in both sexes and castrated males. Discrepancy exits about the existence of these glands in female guinea pigs and knowledge...

  6. Steroid Hormones and Antihormones can Reverse the Castration Induced Stimulation of the Pineal and Adrenal Karyomorphology and Cell Proliferation in Mice (Mus musculus

    Directory of Open Access Journals (Sweden)

    S. Chakraborty

    2011-01-01

    Full Text Available In the present investigation, influence of castration and castrated animals supplemented with steroid hormones and antihormones on pineal-adrenal karyomorphology and dynamics were studied in post pubertal male mice. A group of thirty five mice were orchidectomized and (N = 7 sham operated, were kept in laboratory condition for 30 days. Such castrated were separately supplemented with estradiol at a dose of 5 g, testosterone at a dose of 100 g and antihormones, tamoxifen at a dose of 500 g and flutamide at 2 g daily (all at doses per 100 g.b.w. for ten consecutive days following thirty days of post castration. Present data reveal that both pineal and adrenal gland nuclear size and cell proliferation were significantly increased in thirty days post orchidectomized mice compared to control animals. The values are control pinealocyte nuclear diameter (dim: 4.750.06; castrated pinealocyte nuclear diameter (m: 5.340.04 (p<0.001. Control pineal M% 1.250.07; castrated pineal M% 2.020.11 (p<0.001. In control adrenal, representative of zones was Z. fasciculata nuclear diameter (m (5.110.04; castrated Z. fasciculata nuclear diameter (m 5.410.03 (p<0.001. Control adrenal M% (1.030.06 castrated adrenal M% (1.630.09 p<0.001. It was further observed that such pineal and adrenal stimulation in orchidectomized mice were significantly decreased when orchidectomized mice were administered with steroid hormones (estradiol and testosterone and antihormones (tamoxifen and flutamide compared to orchidectomized mice. Our study indicates that there exists a mutual stimulatory relationship between pineal and adrenal under conditions of steroid deprivation. However, exogenous administration of steroid hormones and antihormones to those castrated mice caused inhibition of these two peripheral endocrine glands.

  7. Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Sha Zhu

    Full Text Available Androgen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the present study were to determine the efficacy somatostatin analogue octreotide (OCT combined with a low dose of docetaxel (DTX using castration resistant prostate cancer cells and to investigate the involved molecular mechanisms in vitro. The anti-proliferative and synergism potential effects were determined by MTT assay. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry. VEGFA, CASP9, CASP3 and ABCB1 gene expression was evaluated by RT-PCR and Q-RT-PCR analysis. OCT in combination with DTX treatments on DU145 cell migration was also evaluated. Investigation revealed that combined administration of DTX and OCT had significant, synergistically greater cytotoxicity than DTX or OCT treatment alone. The combination of the two drugs caused a more marked increase in apoptosis and resulted in greater suppression of invasive potential than either individual agent. There was obvious increase in caspase 3 expression in the OCT alone and two-drug combined treatment groups, however, VEGFA expression was markedly suppressed in them. These results support the conclusion that somatostatin analogues combined with docetaxel may enhance the chemotherapy efficacies through multiple mechanisms in castration-resistant PCa cell line. This work provides a preclinical rationale for the therapeutic strategies to improve the treatment in castrate resistance disease.

  8. Qualidade da carne de novilhos terminados em confinamento e abatidos aos 16 ou 26 meses de idade Meat quality of non-castrate or castrated males feedlot finished and slaughtered at 16 or 26 months of age

    Directory of Open Access Journals (Sweden)

    Fernando Kuss

    2010-04-01

    Full Text Available Avaliaram-se as características sensoriais da carne de novilhos não-castrados ou castrados terminados em confinamento e abatidos aos 16 (superjovens ou 26 (jovens meses de idade. A dieta com relação volumoso:concentrado de 50:50 continha 11,8% de proteína bruta e 2,83 Mcal de energia digestível/kg de matéria seca. A maior amplitude do pH final da carne foi observada nos novilhos jovens e a menor, nos superjovens. A carne dos animais não-castrados, independentemente da idade de abate, foi mais escura, mais grosseira e com menor grau de marmorização em comparação à dos castrados. A carne dos animais castrados teve maior perda de líquidos durante o processo de descongelamento em relação à dos não-castrados (8,55 vs 4,99%. Ocorreu interação entre categoria e sexo do animal para perda de líquido durante a cocção, palatabilidade e suculência. Novilhos jovens não-castrados apresentaram maior quebra à cocção, carne menos palatável e menos suculenta em relação aos jovens castrados e aos superjovens castrados e não-castrados. A redução da idade de abate de 26 para 16 meses de idade, independentemente da condição sexual, melhora a maciez da carne avaliada pelo painel de degustadores.It was evaluated in this work the sensorial characteristics of the meat of non-castrate or castrated males feedlot finished and slaughtered at 16 (young steers or 26 (steers months old. The diet with 50 roughage: 50concentrate contained 11.8% of crude protein and 2.83 Mcal of digestible energy/kg of dry matter. The highest amplitude of the final pH of the meat was noted on the steers, and the lowest on the young steers. The meat of the non-castrate males, regardless to the age at slaughter, was darker, coarser and showed lower marbling degree than the meat of the castrated animals. Thawing loss was higher for the meat of the castrated animals(8.55 vs 4.99%. There was interaction among categories and sex for cooking loss, palatability and

  9. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures

    Directory of Open Access Journals (Sweden)

    Huang Xuan

    2012-07-01

    Full Text Available Abstract Men with metastatic castration-resistant prostate cancer (mCRPC carry poor prognosis despite the use of docetaxel-based regimens which has modest survival benefit shown by randomized clinical trials. Significant progress in the discovery of novel therapeutic agents has been made in the past few years. While sipuleucel-T, cabazitaxel, and abiraterone gained regulatory approval in 2010 and 2011, several highly promising candidates/regimens have failed in large scale clinical trials. Challenges remain to optimize the design and interpretation of clinical trial results and develop more effective strategies for mCRPC. In this review, we examined the positive and negative clinical trials in mCRPC in the past and discussed the various aspects of clinical trial design including selection of targets and appropriate outcome measures, biomarker development and implementation, and strategies for combination therapy.

  10. Abiraterone acetate: A novel drug for castration-resistant prostate carcinoma

    Directory of Open Access Journals (Sweden)

    R Nandha

    2012-01-01

    Full Text Available Androgen-deprivation therapy is the mainstay of treatment for the management of advanced prostate carcinoma till transition to castration-resistant prostate carcinoma (CRPC. Recently, adrenal and intratumoral synthesis of androgens has been found to be the major cause for CRPC. Abiraterone acetate is an orally active, potent and selective inhibitor of 17 a hydroxylase and c 17, 20 lyase, which acts by decreasing the de novo production of androgens with no rise in steroids downstream. Multiple randomized trials have shown significant improvement of >50% decline in prostate-specific antigen (PSA and time to PSA progression (TTPP with abiraterone acetate 1000 mg per day in chemotherapy/ketoconazole treated and naive CRPC patients producing reversible and manageable adverse effects due to mineralocorticoid excess. This article reviews the available evidence on efficacy and safety of this drug in CRPC. Searches of Pubmed, Cochrane database, Medscape, Google and clinicaltrial.org were made for terms like CRPC and abiraterone.

  11. Intraperitoneal administration of gonadotropin-releasing hormone-PE40 induces castration in male rats

    Institute of Scientific and Technical Information of China (English)

    Li Yu; Zhong-Fang Zhang; Chun-Xia Jing; Feng-Lin Wu

    2008-01-01

    AIM: To evaluate the long-term effects of gonadotropin-releasing hormone (GnRH)-based vaccine on levels of GnRH antibody and testosterone, and vaccine-induced immunocastration on sexual behavior of male rats.METHODS: The rats were treated with GnRH-PE40 intraperitoneally every other day for 12 wk. GnRH antibody and testosterone level in rat blood were determined by ELISA and radioimmunoassay, respectively. Morphological changes in testes and sexual behavior of rats were evaluated.RESULTS: GnRH-PE40 induced a high production in GnRH antibody, decreased the serum testosterone level, testis atrophy and sexual function in rats.CONCLUSION: Intraperitoneal administration of GnRH-PE40 produces structural and functional castration of male rat reproductive system by inducing anti-GnRH antibody.

  12. Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    Science.gov (United States)

    Modena, Alessandra; Massari, Francesco; Ciccarese, Chiara; Brunelli, Matteo; Santoni, Matteo; Montironi, Rodolfo; Martignoni, Guido; Tortora, Giampaolo

    2016-08-01

    Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials.

  13. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer.

    Science.gov (United States)

    Fizazi, Karim; Albiges, Laurence; Loriot, Yohann; Massard, Christophe

    2015-01-01

    Androgen deprivation therapy is the standard of care for patients with advanced hormone-sensitive prostate cancer. Despite an initial response, most patients progress to castration-resistant prostate cancer (CRPC). The realization that CRPC remains driven by androgen receptor (AR) signaling has formed the basis for a new generation of agents targeting the AR axis. Two of these agents, abiraterone acetate and enzalutamide, have been shown to prolong overall survival in patients with CRPC. Several other AR inhibitors are currently in development for the treatment of CRPC. The present article reviews ODM-201, a new-generation AR inhibitor with a unique molecular structure, in the treatment of CRPC. The design of an ongoing Phase III trial (ARAMIS) of ODM-201 in men with non-metastatic CRPC is also discussed, at a disease stage for which there is currently no approved treatment. PMID:26313416

  14. Evolving landscape and novel treatments in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Paul J Toren; Martin E Gleave

    2013-01-01

    Treatment options for castrate-resistant prostate cancer (CRPC) have advanced in recent years and significantly improved the outlook for patients with this aggressive and lethal disease.Further understanding of the biologyof CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor (AR) directed therapy.The treatment landscape is rapidly changing and further biologically rationale,biomarker-based ongoing clinical trials are needed.We review the recent results of major clinical trials in CRPC.New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis,microtubules,chaperones,AR and intracellular kinases,as well as immunotherapy,radiopharmaceuticals and bone-targeted agents.The recent improvement in prognosis for CRPC brings continued optimism for further improvements.Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

  15. Physiological and Behavioural Responses in Piglets Submitted to Castration: Preliminary Study

    Directory of Open Access Journals (Sweden)

    Chiara Lonardi

    2011-12-01

    Movement latency was measured for all treatments. Rectal temperature was measured before treatments H and CTD, and 1, 3, 5, 24 hours later. Blood samples for cortisol and lactate determination were collected 1 hour before treatments H and CTD, right after and 3, 5, 24 hours later. The significant increase of movement latency for CTD compared to H showed that pain can be assessed by this type of measure. Rectal temperature was significantly affected by time (P < 0.01 but not by treatment likely due to several factors that might have confounded the studied effect. Cortisol was significantly affected by interaction time*treatment (P < 0.01 particularly due to the high peak for CTD right after the surgical procedure. Lactate was modified only by time (P < 0.01. This preliminary study suggests that a non invasive and easy measure such as movement latency is a promising method to assess pain in piglets after surgical castration and tail docking.

  16. Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Oudard, Stéphane; Kramer, Gero; Caffo, Orazio;

    2015-01-01

    OBJECTIVE: To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients with m......CRPC with a good response to first-line docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status....../pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome. RESULTS: We identified 270 good responders to first-line docetaxel. The median progression-free interval (PFI) was 6 months from the last docetaxel dose...

  17. Challenges in the sequencing of therapies for the management of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Parente, Phillip; Parnis, Francis; Gurney, Howard

    2014-09-01

    Prior to 2010, docetaxel was the standard option for chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Today, the picture is vastly different: several additional therapies have each demonstrated a survival benefit such that we now have chemotherapy (cabazitaxel), androgen suppressive agents (abiraterone acetate and enzalutamide), a cellular vaccine (sipuleucel-T) and radium-233 (for symptomatic bone metastases). With several other agents in the pipeline for late-stage disease, the future looks promising for mCRPC. As the available data are not able to inform as to the optimum sequencing of therapy, this remains a challenge. This paper draws on insights from published and ongoing clinical studies to provide a practical patient-focused approach to maximize the benefits of the current therapeutic armamentarium. Preliminary sequencing suggestions are made based on clinical trial criteria. But until more data become available, clinical gestalt, experience, cost and individual patient preferences will continue to drive choices. PMID:24750803

  18. Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis).

    Science.gov (United States)

    Hayes, Tyrone B; Khoury, Vicky; Narayan, Anne; Nazir, Mariam; Park, Andrew; Brown, Travis; Adame, Lillian; Chan, Elton; Buchholz, Daniel; Stueve, Theresa; Gallipeau, Sherrie

    2010-03-01

    The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines. PMID:20194757

  19. Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Huber, Marie L; Haynes, Laura; Parker, Chris;

    2012-01-01

    Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused...... 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving...... chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately...

  20. A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Archibald M

    2016-01-01

    Full Text Available Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Castrate-resistant prostate cancer (CRPC remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs, sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. Keywords: sorafenib, nilotinib, castrate-resistant prostate cancer, tyrosine kinase inhibitors, nanomedicine

  1. Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2013-06-01

    Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

  2. A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice.

    Science.gov (United States)

    Fokidis, H Bobby; Yieng Chin, Mei; Ho, Victor W; Adomat, Hans H; Soma, Kiran K; Fazli, Ladan; Nip, Ka Mun; Cox, Michael; Krystal, Gerald; Zoubeidi, Amina; Tomlinson Guns, Emma S

    2015-06-01

    Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are

  3. A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice.

    Science.gov (United States)

    Fokidis, H Bobby; Yieng Chin, Mei; Ho, Victor W; Adomat, Hans H; Soma, Kiran K; Fazli, Ladan; Nip, Ka Mun; Cox, Michael; Krystal, Gerald; Zoubeidi, Amina; Tomlinson Guns, Emma S

    2015-06-01

    Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are

  4. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    OpenAIRE

    SATOH, TAKEFUMI; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being ...

  5. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette;

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  6. Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials

    OpenAIRE

    Kaushik, Dharam; Vashistha, Vishal; Isharwal, Sudhir; Sediqe, Soud A.; Lin, Ming-Fong

    2015-01-01

    Historically, androgen-deprivation therapy has been the cornerstone for treatment of metastatic prostate cancer. Unfortunately, nearly majority patients with prostate cancer transition to the refractory state of castration-resistant prostate cancer (CRPC). Newer therapeutic agents are needed for treating these CRPC patients that are unresponsive to androgen deprivation and/or chemotherapy. The histone deacetylase (HDAC) family of enzymes limits the expression of genomic regions by improving b...

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

    OpenAIRE

    Ali Zhang; Jonathan C. Zhao; Jung Kim; Ka-wing Fong; Yeqing Angela Yang; Debabrata Chakravarti; Yin-Yuan Mo; Jindan Yu

    2015-01-01

    SUMMARY 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 ubiquiti...

  8. A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer

    OpenAIRE

    Suzuki, Kazuhiro; Ozono, Seiichiro; Yamaguchi, Akito; Koike, Hidekazu; Matsui, Hiroshi; Nagata, Masao; Takubo, Takatoshi; Miyashita, Kana; Matsushima, Takafumi; Akaza, Hideyuki

    2014-01-01

    Purpose Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC). Methods We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC. Patients received orteronel orally at doses of 200–400 mg twice daily (BID) with or without oral predn...

  9. Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

    OpenAIRE

    Nguyen, Holly M.; Nazanin Ruppender; Xiaotun Zhang; Lisha G. Brown; Gross, Ted S.; Colm Morrissey; Roman Gulati; Vessella, Robert L.; Frauke Schimmoller; Aftab, Dana T.; Eva Corey

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemis...

  10. The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells.

    Science.gov (United States)

    Zhang, Lin; Yang, Shuping; Chen, Xingcheng; Stauffer, Seth; Yu, Fang; Lele, Subodh M; Fu, Kai; Datta, Kaustubh; Palermo, Nicholas; Chen, Yuanhong; Dong, Jixin

    2015-04-01

    Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway. The functional significance of YAP in prostate cancer has remained elusive. In this study, we first show that enhanced expression of YAP is able to transform immortalized prostate epithelial cells and promote migration and invasion in both immortalized and cancerous prostate cells. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2 cells) compared to the level in androgen-sensitive LNCaP cells. Importantly, ectopic expression of YAP activated androgen receptor signaling and was sufficient to promote LNCaP cells from an androgen-sensitive state to an androgen-insensitive state in vitro, and YAP conferred castration resistance in vivo. Accordingly, YAP knockdown greatly reduced the rates of migration and invasion of LNCaP-C4-2 cells and under androgen deprivation conditions largely blocked cell division in LNCaP-C4-2 cells. Mechanistically, we found that extracellular signal-regulated kinase-ribosomal s6 kinase signaling was downstream of YAP for cell survival, migration, and invasion in androgen-insensitive cells. Finally, immunohistochemistry showed significant upregulation and hyperactivation of YAP in castration-resistant prostate tumors compared to their levels in hormone-responsive prostate tumors. Together, our results identify YAP to be a novel regulator in prostate cancer cell motility, invasion, and castration-resistant growth and as a potential therapeutic target for metastatic castration-resistant prostate cancer (CRPC). PMID:25645929

  11. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis

    OpenAIRE

    Kawalec, Paweł; Paszulewicz, Anna; Holko, Przemysław; Pilc, Andrzej

    2012-01-01

    Introduction Sipuleucel-T is a novel active cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). It is assumed to be associated with less adverse events than conventional docetaxel-based chemotherapy. Material and methods A systematic review of literature published between January, 1 1966 and February, 6 2012 was performed to assess the efficacy and safety of sipuleucel-T in patients with mCRPC. Databases were...

  12. Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine

    Directory of Open Access Journals (Sweden)

    O’Connor Erin K

    2012-05-01

    Full Text Available Abstract Background Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine. Methods Pigs received intracoronary infusions of physiologic levels (1–100 nM of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels. Results In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males. Conclusions Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.

  13. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Science.gov (United States)

    Nguyen, Holly M; Ruppender, Nazanin; Zhang, Xiaotun; Brown, Lisha G; Gross, Ted S; Morrissey, Colm; Gulati, Roman; Vessella, Robert L; Schimmoller, Frauke; Aftab, Dana T; Corey, Eva

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. PMID:24205338

  14. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Directory of Open Access Journals (Sweden)

    Holly M Nguyen

    Full Text Available Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa, cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.

  15. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  16. Effect of immunological castration management strategy on lipid oxidation and sensory characteristics of bacon stored under simulated food service conditions.

    Science.gov (United States)

    Herrick, R T; Tavárez, M A; Harsh, B N; Mellencamp, M A; Boler, D D; Dilger, A C

    2016-07-01

    The objectives of this study were to determine the effect of 1) immunological castration (Improvest, a gonadotropin releasing factor analog-diphtheria toxoid conjugate) management strategy (age at slaughter and time of slaughter after second dose) and 2) sex on lipid oxidation and sensory characteristics of bacon stored under simulated food service conditions. For Objective 1, immunological castration management strategies included 24-wk-old immunologically castrated (IC) barrows 4, 6, 8, or 10 wk after the second Improvest dose (ASD); 26-wk-old IC barrows 6 wk ASD; and 28-wk-old IC barrows 8 wk ASD ( = 63). Objective 2 ( = 97) included IC barrows, physically castrated (PC) barrows, and gilts slaughtered at 24, 26, and 28 wks of age. Bellies from 2 slaughter dates were manufactured into bacon under commercial conditions. Bacon slices were laid out on parchment paper, packaged in oxygen-permeable poly-vinyl-lined boxes, and frozen (-33°C) for 1, 4, 8, or 12 wk to simulate food service conditions. At the end of each storage period, bacon was evaluated for lipid oxidation, moisture and lipid content, and sensory characteristics. Data from both objectives were analyzed using the MIXED procedure in SAS with belly as the experimental unit. For both objectives, as storage time increased, lipid oxidation of bacon increased ( evaluated ( ≥ 0.25). For Objective 1, lipid content of bacon from IC barrows increased as time of slaughter ASD increased ( sensory attributes of bacon across management strategies. For the evaluation of sex effects in Objective 2, lipid oxidation was greater ( 0.05). After 12 wk of frozen storage, lipid oxidation values for IC barrows, PC barrows, and gilts were still below 0.5 mg malondialdehyde/kg of meat, the threshold at which trained panelists may deem a food to be rancid. In conclusion, bacon shelf life characteristics were not altered by the immunological castration management strategy and bacon from IC barrows was similar to bacon from

  17. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?

    Science.gov (United States)

    Mita, Alain C; Figlin, Robert; Mita, Monica M

    2012-12-15

    The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support.

  18. Tasquinimod in the treatment of castrate-resistant prostate cancer – current status and future prospects

    Science.gov (United States)

    Mehta, Amit R.; Armstrong, Andrew J.

    2016-01-01

    Treatment options have significantly expanded in recent years for men with metastatic castration-resistant prostate cancer (mCRPC), with the routine use of immunotherapy (sipuleucel-T) and novel hormonal agents such as enzalutamide and abiraterone acetate prior to taxane-based chemotherapy or radium-223 radiotherapy. A number of immune checkpoints limit the immune response of the host to metastatic tumor progression in prostate cancer, one of which is an immunosuppressive and pro-angiogenic cell called the myeloid-derived suppressor cell (MDSC). Tasquinimod is a small molecular oral inhibitor of S100A9, a key cell surface regulator of MDSC function, and has shown anti-angiogenic, antitumor and immune-modulatory properties in preclinical models of prostate cancer and other solid tumors. A large randomized phase II trial of tasquinimod in men with chemotherapy-naïve mCRPC demonstrated a significant prolongation in radiographic and symptomatic progression-free survival compared with placebo, which was also associated with improvements in overall survival. Tasquinimod was studied in a global phase III randomized trial in men with bone mCRPC and, while it significantly improved radiographic progression-free survival, this did not result in an overall survival benefit. However, tasquinimod is under evaluation as well as a combination therapy with other systemic agents in prostate cancer and as a single agent in other solid tumors. This review encompasses the preclinical and clinical development of tasquinimod as a therapy for men with prostate cancer. PMID:26834836

  19. [Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring].

    Science.gov (United States)

    Miller, K; Albers, P; Eichenauer, R; Geiges, G; Grimm, M-O; König, F; Mickisch, G; Pfister, D; Schwentner, C; Suttmann, H; Zastrow, S

    2016-09-01

    Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life. PMID:27411995

  20. Predictors of overall survival in patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    A. S. Markova

    2015-01-01

    Full Text Available Objective: to estimate overall survival (OS rates in patients with metastatic castration-resistant prostate cancer (mCRPC, who have received currently available drugs and to identify the predictors of OS.Subjects and methods. The case histories of 112 patients with mCRPC treated at the N.N. Blokhin Russian Cancer Research Center in 2005 to 2014 were retrospectively analyzed. All the patients had received standard regimens based on docetaxel, cabazitaxel, abiraterone acetate in combination with prednisolone.Results. Whatever the treatment option was, three-year OS rate was 32.0 ± 5.44 %; median survival was 24.3 months. The following poor prognostic factors for OS were pain syndrome; an ECOG performance status score of 2; the levels of prostate-specific antigen ≥ 288 ng/ml, lactate dehydrogenase ≥ 450 U/l, alkaline phosphatase ≥ 250 U/l, calcium < 2.28 mmol/l, and hemoglobin < 11.5 g/dl; as well as < 24 months’ duration of a response to hormonal therapy.Conclusion. The use of standard drug treatment regimen for mCRPC may increase survival in this category of patients to achieve 3-years OV; and the identified factors of OV may aid in choosing treatment policy.

  1. Current paradigms and evolving concepts in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Snmanta Krnmar Pal; Oliver Sartor

    2011-01-01

    @@ Until recently,docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC).The past year and a half has been marked by unprecedented progress in treatments for this disease.Three positive phase III clinical trials have emerged,each evaluating agents (sipuleucel-T,cabazitaxel and abiraterone)with distinct mechanisms of action.Herein,the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC.The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past.We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome.The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.

  2. The relevance of castration and circumcision to the origins of psychoanalysis: 1. The medical context.

    Science.gov (United States)

    Bonomi, Carlo

    2009-06-01

    In this paper the author outlines and discusses the origins and the decline of castration and circumcision as a cure for the nervous and psychic disturbances in women and little girls between 1875 and 1905. The author argues that the opposition to this medical practice affected the conception of hysteria, promoting a distinction between sexuality and the genital organs, and the emergence of an enlarged notion of sexuality, during the period from Freud's medical education to the publication of the Three Essays on the Theory of Sexuality. The hypothesis is put forward that Freud came directly in contact with the genital theory of the neurosis at the time of his training on the nervous disturbances in children with the paediatrician, Adolf Baginsky, in Berlin, in March 1886. It is hypothesized that this experience provoked in Freud an abhorrence of circumcision 'as a cure or punishment for masturbation', prompting an inner confrontation which resulted in a radical reorganization of the way of thinking about sexuality. It is also suggested that this contributed to Freud developing a capacity to stay with contradictions, something which would become a central quality of the psychoanalytic attitude. PMID:19580597

  3. Castration resistant prostate cancer (CRPC): state of the art, perspectives and new challenges.

    Science.gov (United States)

    Massari, Francesco; Maines, Francesca; Modena, Alessandra; Brunelli, Matteo; Bria, Emilio; Artibani, Walter; Martignoni, Guido; Tortora, Giampaolo

    2013-07-01

    The rapid approval of several novel agents has given prostate cancer patients and their treating physicians many new and effective therapeutic options. Four new medical therapies were recently approved on the basis of prolonged overall survival in castration-resistant prostate cancer (CRPC) patients: sipuleucel-T, cabazitaxel, abiraterone acetate and MDV3100. Additionally, there are several other promising prostate cancer agents in late-stage development, including PROSTVAC-VF, orteronel and radium-223 chloride, each with a novel mechanism of action. The treatment paradigm for these patients is rapidly evolving, with future study needed to define the optimal sequencing and potential combinations of these new agents. In this review, we discuss the recent progress in understanding the biology of this disease and examining the development of a variety of new agents with promising activity and a favorable toxicity profile, that have been investigated in the setting of hormonal, cytotoxic, immune and targeted therapy. In this new therapeutic setting of CRPC, clinicians will have an opportunity to balance benefits and harms of these new agents in an individual context.

  4. Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

    Directory of Open Access Journals (Sweden)

    Joelle El-Amm

    2013-01-01

    Full Text Available Majority of patients with metastatic castrate resistant prostate cancer (mCRPC develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs. Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

  5. Experience with octreotide depot in the treatment of castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    G. P. Kolesnikov

    2015-01-01

    Full Text Available Castration-resistant prostate cancer (CRPC is one of the most complex and unsolved problems in urologic oncology. The somatostatin analogue octreotide depot made in Russia may be used for its treatment. The paper gives the results of a trial of the efficiency and safety of treatment with octreotide depot 30 mg and dexamethasone in 20 patients aged 58 to 89 years with CRPC during continued androgen deprivation therapy. The duration of the trial was 3 months. A response was assessed from the serum levels of prostate-specific antigen (PCA, the time course of changes in general and biochemical blood test values, the degree of pain syndrome, and improvement in quality of life in a patient. A total response in reducing PSA was obtained in 70 % of the patents; overall, the best results were achieved in the group receiving octreotide before chemotherapy with docetaxel. The tolerability of octreotide deport with dexamethasone was good in all cases; no obvious adverse hematological and clinical reactions were noted.

  6. Economic evaluation of sipuleucel-T immunotherapy in castration-resistant prostate cancer.

    Science.gov (United States)

    Holko, Przemysław; Kawalec, Paweł

    2014-01-01

    The objective is to examine the cost-utility of sipuleucel-T immunotherapy in asymptomatic or minimally symptomatic castration-resistant prostate cancer patients. The addition of sipuleucel-T immunotherapy to standard treatment led to a gain of 0.37 quality-adjusted life-year (QALY) at an additional cost of US$104,536. The incremental cost-utility ratio was US$283,000 per QALY saved. Threshold sensitivity analyses indicated that a price reduction of at least 53%, or application in a group of patients resulting in the relative reduction in the mortality rate of at least 39%, ought to augment the economic value of this regimen. Sipuleucel-T immunotherapy treatment at the current price with 96.5% certainty is not cost-effective. The specific group of patients who will benefit more from the treatment should be revealed and treated, or the cost of the vaccine should be lowered significantly to increase its economic value. Accounting for crossover treatment in control patients improves sipuleucel-T's value (US$132,000 per QALY saved) although further investigation is necessary.

  7. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    International Nuclear Information System (INIS)

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats

  8. Castration induces up-regulation of intratumoral androgen biosynthesis and androgen receptor expression in an orthotopic VCaP human prostate cancer xenograft model.

    Science.gov (United States)

    Knuuttila, Matias; Yatkin, Emrah; Kallio, Jenny; Savolainen, Saija; Laajala, Teemu D; Aittokallio, Tero; Oksala, Riikka; Häkkinen, Merja; Keski-Rahkonen, Pekka; Auriola, Seppo; Poutanen, Matti; Mäkelä, Sari

    2014-08-01

    Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration). Tumor growth was monitored through weekly serum prostate-specific antigen measurements, and mice with recurrent tumors after castration were randomized to treatment groups. Serum prostate-specific antigen concentrations showed significant correlation with tumor volume. Castration-resistant tumors retained concentrations of intratumoral androgen (androstenedione, testosterone, and 5α-dihydrotestosterone) at levels similar to tumors growing in intact hosts. Accordingly, castration induced up-regulation of enzymes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. The AR antagonists enzalutamide (MDV3100) and ARN-509 suppressed PSA production of castration-resistant tumors, confirming the androgen dependency of these tumors. Taken together, the findings demonstrate that our VCaP xenograft model exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC.

  9. Effect of daily treatment with Thai herb, Kaempferia parviflora, in Hershberger assay using castrated immature rats.

    Science.gov (United States)

    Trisomboon, Hataitip; Watanabe, Gen; Wetchasit, Phongphat; Taya, Kazuyoshi

    2007-04-01

    The aim of the present study was to investigate the testosterone-like effect of Kaempferia parviflora (KP). Castrated immature rats were randomized and divided into two groups (control and KP-treatment groups). The rats (n=7-8) were treated daily for 5 days by oral route with water in the control group and 1,000 mg/kg of KP in the treatment group. All rats were decapitated 24 h after their last dose and then blood samples were collected for assay of serum FSH, LH, testosterone, progesterone and corticosterone levels. The seminal vesicles plus coagulating glands, ventral prostate, levator ani muscle plus bulbocavernosus muscle, glans penis, kidneys and the adrenal glands were collected and weighed for organ wet weight. Body weight and weight of food intake were recorded throughout the study period. The results show that relative body weight gain in the KP-treatment group was significantly increased 24 and 48 h after the first dose (P<0.05) and then was indistinguishable from the control group. There were no significant differences in the relative reproductive and non-reproductive organ weights between the groups, although all organ weights, except for the glans penis, tended to increase in the KP-treatment group. The serum testosterone levels were significantly increased in the KP-treatment group. There were no significant differences in the serum FSH, LH, progesterone, or corticosterone levels between the groups, even though the serum progesterone level tended to increase and serum LH level tended to decrease in the KP-treatment group. The present study indicates that KP has no testosterone-like effect on reproduction in male rats. PMID:17179656

  10. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Mark N Stein; Neal Patel; Alexander Bershadskiy; Alisa Sokoloff; Eric A Singer

    2014-01-01

    Suppression of gonadal testosterone synthesis represents the standard ifrst line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer (CRPC), it is possible to detect persistent activation of the androgen receptor (AR) through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17α-hydroxylase and 17,20-lyase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a signiifcant improvement in overall survival (OS) with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased speciifcity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors;recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents;and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone beneift or restore abiraterone activity.

  11. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer.

  12. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  13. Sedation with Xylazine-Diazepam and Epidural Administration of Lidocaine and Xylazine for Castration and Ovariohysterectomy in Cats

    Directory of Open Access Journals (Sweden)

    Bizhan Ziaei

    2010-06-01

    Full Text Available The aim of this study was to determine whether anesthesia consisting of sedation induced by intramuscular administration of xylazine-diazepam and lumbosacral analgesia induced by epidural administration of lidocaine and xylazine is satisfactory for castration and ovariohysterectomy in cats. Six adult (3 male and 3 female, 2.5 ± 0.5 years of age cats (mean body weight ± SD, 2.2 ± 0.44 kg were used in this study. Cats were sedated with xylazine (1-2 mg kg-1 IM and diazepam (0.2 mg kg-1, IM and 5 minutes later a 2% solution of lidocaine (0.5ml/4.5kg and xylazine (1 mg kg-1 were administered into the lumbosacral epidural space. Open castration technique or ventral midline routine ovariohysterectomy were performed. Time to onset, duration and cranial spread of analgesia were recorded. Heart rate, respiratory rate and rectal temperature were recorded at time 0 (prior to epidural drugs administration as a base line values and at 10, 20, 30, 45 and 60 minutes after the epidural administration. Onset time of analgesia was 4.0 ± 0.63 min (Mean ± SEM and duration of analgesia was 89.5 ± 3.0 min (Mean ± SEM. However, surgical procedures were completed within 25-37 min. There were significant decrease in heart rate and rectal temperature values and significant increase in respiratory rate (P < 0.001. Intramuscular administration of xylazine-diazepam for sedation and epidural administration of lidocaine and xylazine for analgesia provided satisfactory analgesia for castration and ovariohysterectomy in cats. Utilizing epidural anesthetic technique with this combination is most useful for spaying surgery, especially when the surgical procedure can be completed in < 40 minutes.

  14. Lean meat prediction with HGP, CGM and CSB-Image-Meater, with prediction accuracy evaluated for different proportions of gilts, boars and castrated boars in the pig population.

    Science.gov (United States)

    Engel, B; Lambooij, E; Buist, W G; Vereijken, P

    2012-02-01

    Prediction equations for the percentage lean meat in pig carcasses in The Netherlands were derived for the Hennessy Grading Probe 7, Capteur Gras/Maigre--Sydel and CSB-Image-Meater. Because castrated males are expected to vanish from the Dutch pig population in the near future, accuracy of prediction was evaluated for different scenarios representing a wide range of different proportions for entire males, castrated males and females in the Dutch pig population. The prediction equations for the instruments are in compliance with the EC regulations for prediction accuracy for the different scenarios. So, these equations will remain valid when castrated males are (gradually) removed from the Dutch slaughter population. Results of this study are of interest for researchers from countries or areas contemplating the use of one of the aforementioned instruments. The statistical approach for evaluation of prediction accuracy is of particular interest when changes in proportions of important subpopulations in the target population are foreseen. PMID:21871739

  15. Lean meat prediction with HGP, CGM and CSB-Image-Meater, with prediction accuracy evaluated for different proportions of gilts, boars and castrated boars in the pig population.

    Science.gov (United States)

    Engel, B; Lambooij, E; Buist, W G; Vereijken, P

    2012-02-01

    Prediction equations for the percentage lean meat in pig carcasses in The Netherlands were derived for the Hennessy Grading Probe 7, Capteur Gras/Maigre--Sydel and CSB-Image-Meater. Because castrated males are expected to vanish from the Dutch pig population in the near future, accuracy of prediction was evaluated for different scenarios representing a wide range of different proportions for entire males, castrated males and females in the Dutch pig population. The prediction equations for the instruments are in compliance with the EC regulations for prediction accuracy for the different scenarios. So, these equations will remain valid when castrated males are (gradually) removed from the Dutch slaughter population. Results of this study are of interest for researchers from countries or areas contemplating the use of one of the aforementioned instruments. The statistical approach for evaluation of prediction accuracy is of particular interest when changes in proportions of important subpopulations in the target population are foreseen.

  16. Response of male mice to odours of female mice in different stages of oestrous cycle: self-grooming behaviour and the effect of castration.

    Science.gov (United States)

    Achiraman, Shanmugam; SankarGanesh, Devaraj; Kannan, Soundarapandian; Kamalakkannan, Soundararajan; Nirmala, Natarajan; Archunan, Govindaraju

    2014-01-01

    The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours.

  17. Development of a preliminary nomogram to predict progression of bone scan for castration-resistant prostate cancer

    OpenAIRE

    Lin GW; Ye DW; Jia HX; Dai B; Zhang HL; Zhu Y; Shi GH; Ma CG

    2015-01-01

    Guo-Wen Lin,1,2 Ding-Wei Ye,1,2 Hui-Xun Jia,2,3 Bo Dai,1,2 Hai-Liang Zhang,1,2 Yao Zhu,1,2 Guo-Hai Shi,1,2 Chun-Guang Ma1,2 1Department of Urology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, 3Department of Clinical Statistics Center, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China Abstract: The optimal time to perform bone scan to detect new metastasis during the castration-re...

  18. Androgen Deprivation Therapy and Secondary Hormone Therapy in the Management of Hormone-sensitive and Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Saad, Fred; Fizazi, Karim

    2015-11-01

    Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer (mPC). However, nearly all patients with mPC progress to castration-resistant PC (CRPC). Arrays of treatments, including secondary hormonal therapies, are available for the treatment of mPC and CRPC, which show efficacy when administered with ADT. Continuation of ADT is recommended for CRPC treatment as therapies are added. New secondary hormonal therapies include abiraterone, targeting the CYP17 enzyme family, and enzalutamide, an androgen receptor inhibitor with heightened binding specificity. The optimal decision-making process for CRPC treatment option remains unclear, pending further research and experience. PMID:26282624

  19. Sedation with Xylazine-Diazepam and Epidural Administration of Lidocaine and Xylazine for Castration and Ovariohysterectomy in Cats

    OpenAIRE

    Bizhan Ziaei; Zahra Shafiei; Mohammad Shadkhast; Amin Bigham-Sadegh

    2010-01-01

    The aim of this study was to determine whether anesthesia consisting of sedation induced by intramuscular administration of xylazine-diazepam and lumbosacral analgesia induced by epidural administration of lidocaine and xylazine is satisfactory for castration and ovariohysterectomy in cats. Six adult (3 male and 3 female, 2.5 ± 0.5 years of age) cats (mean body weight ± SD, 2.2 ± 0.44 kg) were used in this study. Cats were sedated with xylazine (1-2 mg kg-1 IM) and diazepam (0.2 mg kg-1, IM) ...

  20. Physical castration and inmunocastration of early-naturing bulls fed high concetrate diets welfare, performance, and carcass and meat quality /

    OpenAIRE

    Martí Rodríguez, Sònia

    2012-01-01

    La castració de vedells ha estat proposada com a mètode de millora de la qualitat de la canal i de la carn. Tot i això, la preocupació pel benestar animal, el control del dolor que pugui estar associat i el seu impacte en els paràmetres productius i la qualitat de la carn dels vedells, posen de manifest la necessitat de que sigui revisada. Del primer capítol d’aquesta tesis es pot concloure que tot i que el creixement dels vedells castrats es veu afectat i que alguns paràmetres comportamental...

  1. Castration-resistant prostate cancer (CRPC):the rise and fall of systemic chemotherapy. Shadows of recent phase 3 studies

    Institute of Scientific and Technical Information of China (English)

    Omar Abdel-Rahman

    2014-01-01

    Castration-resistant prostate cancer (CRPC) is defined as prostate cancer that recurs while a patient is receiving androgen deprivation therapy (ADT). Many treatment options have been suggested for this chal enging disease;starting from 2-year hormonal manipulations, mitoxantrne-and docetaxel-based regimens reaching to the overwhelming new systemic op-tions for CRPC (newer hormonal treatments, cytotoxic chemotherapies, bone-targeted agents and immunotherapeutics);and the question is:do the traditional cytotoxic regimens stil have a role amidst al these new options?

  2. ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors

    Directory of Open Access Journals (Sweden)

    Shinichi Yamashita

    2012-01-01

    Full Text Available Early studies suggested androgen receptor (AR splice variants might contribute to the progression of prostate cancer (PCa into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrated the in vivo therapeutic effects of ASC-J9 by showing the inhibition of PCa growth using the xenografted model of CWR22Rv1 cells orthotopically implanted into castrated nude mice with undetectable serum testosterone. These results suggested that targeting both fAR- and AR3-mediated PCa growth by ASC-J9 may represent the novel therapeutic approach to suppress castration-resistant PCa. Successful clinical trials targeting both fAR and AR3 may help us to battle castration-resistant PCa in the future.

  3. Androgen Receptor Expression and Cellular Proliferation During Transition from Androgen-Dependent to Recurrent Growth after Castration in the CWR22 Prostate Cancer Xenograft

    OpenAIRE

    Kim, Desok; Gregory, Christopher W.; French, Frank S.; Smith, Gary J.; Mohler, James L.

    2002-01-01

    Androgen receptor expression was analyzed in the CWR22 human prostate cancer xenograft model to better understand its role in prostate cancer recurrence after castration. In androgen-dependent tumors, 98.5% of tumor cell nuclei expressed androgen receptor with a mean optical density of 0.26 ± 0.01. On day 2 after castration androgen deprivation decreased immunostained cells to 2% that stained weakly (mean optical density, 0.16 ± 0.08). Cellular proliferation measured using Ki-67 revealed

  4. A Phase 2 Trial of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer and without Prior Chemotherapy (JPN-201 Study)

    OpenAIRE

    Matsubara, Nobuaki; Uemura, Hirotsugu; SATOH, TAKEFUMI; Suzuki, Hiroyoshi; Nishiyama, Tsutomu; Uemura, Hiroji; Hashine, Katsuyoshi; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicent...

  5. Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

    Science.gov (United States)

    Zhao, Jing; Liu, Ge-Li; Wei, Ying; Jiang, Li-Hong; Bao, Peng-Li; Yang, Qing-Yan

    2016-09-01

    The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked

  6. Racemic ketamine in comparison to S-ketamine in combination with azaperone and butorphanol for castration of pigs.

    Science.gov (United States)

    Bettschart-Wolfensberger, R; Stauffer, S; Hässig, M; Flaherty, D; Ringer, S K

    2013-12-01

    In this prospective blinded randomised study, 28 male 9 week old pigs of bodyweight 25 kg, were anaesthetised for castration using 5 mg/kg azaperone, 0.2 mg/kg butorphanol and 0.4 mg/kg meloxicam, in conjunction with either 15 mg/kg racemic ketamine (Keta-Race) or 9 mg/kg S-ketamine (S-Keta), all drugs being injected intramuscularly. Anaesthesia induction, maintenance and recovery were timed and scored. Insufficient anaesthesia was supplemented with ¼ the initial dose of ketamine or S-ketamine, respectively, administered intravenously. A t-test was utilised for analysis of timings, and, for repeated recovery time data, ANOVA was used. In relation to quantification and timing of supplemental drug doses, a chi square test was used and the scoring was analysed by two sample Wilcoxon rank-sum test. Ketamine re-dosing was required in 23 animals on a total of 46 occasions distributed evenly throughout both groups. The only group differences occurred during recovery, with the S-Keta group showing earlier movements, sternal recumbency and ability to stand. Three pigs in each group showed muscle fasciculations during the recovery period, while an additional two animals of the Keta-Race group exhibited marked and unacceptable paddling in recovery. In conclusion, S-ketamine at a dose rate of 60 % of that of racemic ketamine induced comparable anaesthesia for castration in pigs, but with superior recovery characteristics.

  7. Effect of castration on carcass quality and differential gene expression of longissimus muscle between steer and bull.

    Science.gov (United States)

    Zhou, Zheng-Kui; Gao, Xue; Li, Jun-Ya; Chen, Jin-Bao; Xu, Shang-Zhong

    2011-11-01

    The effect of castration on carcass quality was investigated by ten Chinese Simmental calves. Five calves were castrated randomly at 2 months old and the others were retained as normal intact bulls. All animals were slaughtered at 22 months old. The results showed that bulls carcass had higher weight (P < 0.05), dressing percentages and bigger longissimus muscle areas (P < 0.05) than steers. But steer meat had lower shear force values and was fatter (P < 0.05) than bull. Furthermore, in order to discover genes that were involved in determining steer meat quality, we compared related candidate gene expression in longissimus muscle between steer (tester) and bull (driver) using suppressive subtractive hybridization. Ten genes were identified as preferentially expressed in longissimus muscle of steer. The expression of four selected differentially expressed genes was confirmed by quantitative real-time PCR. Overall, a 1.96, 2.41, 2.89, 2.41-fold increase in expression level was observed in steer compared with bull for actin, gamma 2, smooth muscle, tropomyosin-2, insulin like growth factor 1 and hormone-sensitive lipase, respectively. These results implied that these differentially expressed genes could play an important role in the regulation of steer meat quality. PMID:21253852

  8. Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

    International Nuclear Information System (INIS)

    Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis

  9. Overexpression of the potential kinase serine/ threonine/tyrosine kinase 1 (STYK 1) in castration-resistant prostate cancer.

    Science.gov (United States)

    Chung, Suyoun; Tamura, Kenji; Furihata, Mutsuo; Uemura, Motohide; Daigo, Yataro; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Nakamura, Yusuke; Nakagawa, Hidewaki

    2009-11-01

    Despite high response rates and clinical benefits, androgen ablation often fails to cure advanced or relapsed prostate cancer because castration-resistant prostate cancer (CRPC) cells inevitably emerge. CRPC cells not only grow under castration, but also behave more aggressively, indicating that a number of malignant signaling pathways are activated in CRPC cells as well as androgen receptor signaling. Based on information from the gene expression profiles of clinical CRPC cells, we here identified one overexpressed gene, serine/threonine/tyrosine kinase 1 (STYK1), encoding a potential kinase, as a molecular target for CRPC. RNA and immunohistochemical analyses validated the overexpression of STYK1 in prostate cancer cells, and its expression was distinct in CRPC cells. Knockdown of STYK1 by siRNA resulted in drastic suppression of prostate cancer cell growth and, concordantly, enforced expression of STYK1 promoted cell proliferation, whereas ectopic expression of a kinase-dead mutant STYK1 did not. An in vitro kinase assay using recombinant STYK1 demonstrated that STYK1 could have some potential as a kinase, although its specific substrates are unknown. These findings suggest that STYK1 could be a possible molecular target for CRPC, and small molecules specifically inhibiting STYK1 kinase could be a possible approach for the development of novel CRPC therapies.

  10. Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, C.C.S. [Disciplina de Nefrologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Tovar, A.M.F. [Laboratório de Tecido Conjuntivo, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Guimarães, M.A.M. [Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Bregman, R. [Disciplina de Nefrologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

    2013-08-10

    Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

  11. Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

    Directory of Open Access Journals (Sweden)

    Gater Adam

    2011-10-01

    Full Text Available Abstract Background Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC. Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited. Methods To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL, semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI scale from the McGill Pain Questionnaire (MPQ, and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF was also assessed. Results Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients. Conclusions Study findings support the

  12. Docetaxel-related toxicity in metastatic hormone-sensitive and metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Schweizer, Michael T; Gulati, Roman; Mostaghel, Elahe A; Nelson, Peter S; Montgomery, R Bruce; Yu, Evan Y; Cheng, Heather H

    2016-07-01

    Docetaxel plus androgen deprivation therapy (ADT) offers a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, one trial evaluating docetaxel in mHSPC (GETUG-AFU15) showed unexpected toxicity; raising concerns that docetaxel may carry increased toxicity when used to treat mHSPC compared to metastatic castration-resistant prostate cancer (mCRPC). We conducted a retrospective analysis evaluating differences in toxicity based on the clinical state (i.e., mHSPC vs. mCRPC) that docetaxel was used. Patients initiating docetaxel between 1/1/2014 and 7/15/2015 were included, with the former date chosen to coincide with the press release for the first mHSPC study that showed a survival benefit with early docetaxel; ensuring contemporary docetaxel-treated cohorts. Thirty-nine mCRPC and 22 mHSPC patients were included. Compared to mCRPC, mHSPC patients were younger (median years: 66.3 vs. 71.8, P = 0.007); had better performance status (ECOG 0-1: 100 vs. 62 %, P < 0.0001); and used opiates less frequently (29 vs. 66 %, P = 0.04). Neutropenic fevers occurred in 9 and 5 % (P = 0.95) of men with mHSPC and mCRPC, respectively. Other toxicities also occurred at similar rates between cohorts. The incidence of any toxic event was 73 and 67 % (P = 0.84) for men with mHSPC and mCRPC, respectively. Within the mHSPC cohort, neutropenic fevers occurred at a similar rate regardless of the time interval between initiating ADT and the start of docetaxel. We did not observe a significant difference in toxicity between mHSPC and mCRPC patients receiving docetaxel. However, the small sample size and retrospective nature of this study limit our ability to draw definitive conclusions. PMID:27300548

  13. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy

    NARCIS (Netherlands)

    Harland, S.; Staffurth, J.; Molina, A.; Hao, Y.; Gagnon, D.D.; Sternberg, C.N.; Cella, D.; Fizazi, K.; Logothetis, C.J.; Kheoh, T.; Haqq, C.M.; Bono, J.S. de; Scher, H.I.; Mulders, P.F.

    2013-01-01

    BACKGROUND: In a recent randomised, double-blind, phase III clinical trial among 1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly prolong overall survival compared with prednisone alone. H

  14. Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naive Patients with Metastatic Castration Resistant Prostate Cancer

    NARCIS (Netherlands)

    Smith, M.R.; Rathkopf, D.E.; Mulders, P.F.A.; Carles, J.; Poppel, H. Van; Li, J.; Kheoh, T.; Griffin, T.W.; Molina, A.; Ryan, C.J.

    2015-01-01

    PURPOSE: Metastatic castration resistant prostate cancer primarily affects elderly men. In this post hoc analysis we investigated the safety and efficacy of abiraterone acetate in elderly (age 75 years or greater) and younger (less than 75 years) patient subgroups at the prespecified interim analysi

  15. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

    DEFF Research Database (Denmark)

    de Bono, Johann Sebastian; Oudard, Stephane; Ozguroglu, Mustafa;

    2010-01-01

    Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer with progre...

  16. Androgen receptor splice variant 7 (AR-V7) and drug efficacy in castration-resistant prostate cancer: Biomarker for treatment selection exclusion or inclusion?

    Science.gov (United States)

    Leibrand, Crystal R; Price, Douglas K; Figg, William D

    2016-05-01

    Currently there are no molecular biomarkers used to help guide treatment selection for those patients with castration-resistant prostate cancer. A recent study published in JAMA Oncology (Antonarakis et al.) presents evidence supporting the potential use of androgen receptor splice variant 7 as a biomarker for optimal treatment selection in this population.

  17. Aldo-keto reductase family 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer

    NARCIS (Netherlands)

    Hamid, A.R.A.H.; Pfeiffer, M.J.; Verhaegh, G.W.C.T.; Schaafsma, H.E.; Brandt, A.; Sweep, F.C.; Sedelaar, J.P.M.; Schalken, J.A.

    2012-01-01

    Current endocrine treatment for advanced prostate cancer does not result in a complete ablation of adrenal androgens. Adrenal androgens can be metabolized by prostate cancer cells, which is one of the mechanisms associated with progression to castration-resistant prostate cancer (CRPC). Aldo-keto re

  18. Using Castration Surgery in Male Rats to Demonstrate the Physiological Effects of Testosterone on Seminal Vesicle Anatomy in an Undergraduate Laboratory Setting

    Science.gov (United States)

    Belanger, Rachelle M.; Conant, Stephanie B.; Grabowski, Gregory M.

    2013-01-01

    Rats can be used as a model organism to teach physiological concepts in a laboratory setting. This article describes a two-part laboratory that introduces students to hypothesis testing, experimental design, the appropriate use of controls and surgical techniques. Students perform both a castration and sham-control surgery on male rats and test…

  19. Lean meat prediction with HGP, CGM and CSB-Image-Meater, with prediction accuracy evaluated for different proportions of gilts, boars and castrated boars in the pig population

    NARCIS (Netherlands)

    Engel, B.; Lambooij, E.; Buist, W.G.; Vereijken, P.F.G.

    2012-01-01

    Prediction equations for the percentage lean meat in pig carcasses in The Netherlands were derived for the Hennessy Grading Probe 7, Capteur Gras/Maigre - Sydel and CSB-Image-Meater. Because castrated males are expected to vanish from the Dutch pig population in the near future, accuracy of predicti

  20. Surgical castration but not immuncastration is associated with reduced hypothalamic GnIH and GHRH/GH/IGF-I axis function in male rats.

    Science.gov (United States)

    Han, Xingfa; Li, Junli; Cao, Xiaohan; Du, Xiaogang; Meng, Fengyan; Zeng, Xianyin

    2016-07-15

    Gonadotropin-inhibitory hormone (GnIH) is a potent positive regulator of the growth axis. The present study was aimed to comparatively investigate the effects of surgical and immunologic castration on hypothalamic GnIH expression and endocrine function of the growth axis. Thirty-six prepubertal male rats were randomly allocated into three groups (n = 12): control, surgically castrated or immunized against 100-μg D-Lys6-GnRH-tandem peptide conjugated to ovalbumin in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples were collected (for hormone and urea nitrogen concentrations) at 2-week intervals, and growth performance was evaluated. Compared to intact controls, surgical castration reduced (P hormone-releasing hormone (GHRH), pituitary growth hormone (GH), and liver insulin-like growth factor-1 (IGF-1), reduced (P GH and IGF-1 and increased (P GH, and the serum concentrations of GH (P > 0.05). Moreover, serum concentrations of IGF-1 and urea nitrogen in immunocastrates were substantially higher and lower than those in surgical castrates, respectively (P GH/IGF-I axis function in male rats. PMID:27020878

  1. Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan;

    2014-01-01

    PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg...

  2. 去势对雄性大鼠心肌结构的影响%Influence of castration on myocardial structure of male rats

    Institute of Scientific and Technical Information of China (English)

    施超; 李艳香; 翟华玲; 姜博仁; 郭明皓; 陆颖理

    2011-01-01

    Objective To investigate the influence of low androgen on myocardial structure of male rats. Methods Male SD rats were randomly divided into control group (n =8), castration group (n =7) and androgen replacement group (n =8). Rats in control group underwent sham castration, those in castration group were castrated, and those in replacement group were given testosterone undecanoate after castration. Ten weeks later, serum concentration of testosterone was measured by radioimmunoassay. Pathological changes of myocardial tissues were observed by light microscopy and electron microscopy. Results Serum concentration of testosterone in castration group was significantly lower than those in control group and androgen replacement group (P < 0. 01). Light microscopy revealed that in castration group, there were myocardial swelling, hypertrophy, degeneration and nucleus enlargement, the nuclei significantly enlarged, the myocardial fibers fractured, dissolved, contracted and became wavy, and arranged in disorder. Electron microscopy revealed that in castration group, myocardial fibers arranged irregularly, fractured and dissolved, the glycogen and flat drop between muscle fibers accumulated, mitochondria swelled, most of the ridges in mitochondria were not clear, and the intercalated disk widened. Compared with castration group, the above-mentioned pathological changes in androgen replacement group were significantly lessened. Conclusion Obvious myocardial histopathological injury may occur in male rats after castration, and exogenous testosterone replacement therapy may work in some degree. Low androgen may do harm to myocardium of males.%目的 研究低雄激素对心肌组织结构的影响.方法 雄性SD大鼠随机分为对照组(n=8)、去势组(n=7)和雄激素替代组(n=8).对照组进行假去势手术;去势组进行去势手术;雄激素替代组进行去势手术后肌肉注射十一酸睾酮替代治疗.10周后取各组大鼠血清,放射免疫法测定

  3. CH5137291, an androgen receptor nuclear translocation-inhibiting compound, inhibits the growth of castration-resistant prostate cancer cells.

    Science.gov (United States)

    Ishikura, Nobuyuki; Kawata, Hiromitsu; Nishimoto, Ayako; Nakamura, Ryo; Tsunenari, Toshiaki; Watanabe, Miho; Tachibana, Kazutaka; Shiraishi, Takuya; Yoshino, Hitoshi; Honma, Akie; Emura, Takashi; Ohta, Masateru; Nakagawa, Toshito; Houjo, Takao; Corey, Eva; Vessella, Robert L; Aoki, Yuko; Sato, Haruhiko

    2015-04-01

    Resistance of prostate cancer to castration is currently an unavoidable problem. The major mechanisms underlying such resistance are androgen receptor (AR) overexpression, androgen-independent activation of AR, and AR mutation. To address this problem, we developed an AR pure antagonist, CH5137291, with AR nuclear translocation-inhibiting activity, and compared its activity and characteristics with that of bicalutamide. Cell lines corresponding to the mechanisms of castration resistance were used: LNCaP-BC2 having AR overexpression and LNCaP-CS10 having androgen-independent AR activation. VCaP and LNCaP were used as hormone-sensitive prostate cancer cells. In vitro functional assay clearly showed that CH5137291 inhibited the nuclear translocation of wild-type ARs as well as W741C- and T877A-mutant ARs. In addition, it acted as a pure antagonist on the transcriptional activity of these types of ARs. In contrast, bicalutamide did not inhibit the nuclear translocation of these ARs, and showed a partial/full agonistic effect on the transcriptional activity. CH5137291 inhibited cell growth more strongly than bicalutamide in VCaP and LNCaP cells as well as in LNCaP-BC2 and LNCaP-CS10 cells in vitro. In xenograft models, CH5137291 strongly inhibited the tumor growth of LNCaP, LNCaP-BC2, and LNCaP-CS10, whereas bicalutamide showed a weaker effect in LNCaP and almost no effect in LNCaP-BC2 and LNCaP-CS10 xenografts. Levels of prostate-specific antigen (PSA) in plasma correlated well with the antitumor effect of both agents. CH5137291 inhibited the growth of LNCaP tumors that had become resistant to bicalutamide treatment. A docking model suggested that CH5137291 intensively collided with the M895 residue of helix 12, and therefore strongly inhibited the folding of helix 12, a cause of AR agonist activity, in wild-type and W741C-mutant ARs. In cynomolgus monkeys, the serum concentration of CH5137291 increased dose-dependently and PSA level decreased 80% at 100 mg/kg. CH

  4. Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space

    Directory of Open Access Journals (Sweden)

    Sartor A Oliver

    2011-04-01

    Full Text Available Abstract Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC. Despite this designation, however, there is evidence that androgen receptor (AR-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 demonstrated that docetaxel chemotherapy could significantly improve survival. These results established first-line docetaxel as the standard of care for mCRPC. After resistance to further docetaxel therapy develops, treatment options were once again limited. Recently reported results from phase 3 trials have shown that additional therapy with the novel taxane cabazitaxel (with prednisone, or treatment with the antiandrogen abiraterone (with prednisone could improve survival for patients with mCRPC following docetaxel therapy. Compared with mitoxantrone/prednisone, cabazitaxel/prednisone significantly improved overall survival, with a 30% reduction in rate of death, in patients with progression of mCRPC after docetaxel therapy in the TROPIC trial. Similarly, abiraterone acetate (an inhibitor of androgen biosynthesis plus prednisone significantly decreased the rate of death by 35% compared with placebo plus prednisone in mCRPC patients progressing after prior docetaxel therapy in the COU-AA-301 trial. Results of these trials have thus established two additional treatment options for mCRPC patients in the "post-docetaxel space." In view of the continued AR

  5. Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space.

    Science.gov (United States)

    Sartor, A Oliver

    2011-04-23

    Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC). Despite this designation, however, there is evidence that androgen receptor (AR)-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 demonstrated that docetaxel chemotherapy could significantly improve survival. These results established first-line docetaxel as the standard of care for mCRPC. After resistance to further docetaxel therapy develops, treatment options were once again limited. Recently reported results from phase 3 trials have shown that additional therapy with the novel taxane cabazitaxel (with prednisone), or treatment with the antiandrogen abiraterone (with prednisone) could improve survival for patients with mCRPC following docetaxel therapy. Compared with mitoxantrone/prednisone, cabazitaxel/prednisone significantly improved overall survival, with a 30% reduction in rate of death, in patients with progression of mCRPC after docetaxel therapy in the TROPIC trial. Similarly, abiraterone acetate (an inhibitor of androgen biosynthesis) plus prednisone significantly decreased the rate of death by 35% compared with placebo plus prednisone in mCRPC patients progressing after prior docetaxel therapy in the COU-AA-301 trial. Results of these trials have thus established two additional treatment options for mCRPC patients in the "post-docetaxel space." In view of the continued AR-mediated signaling on m

  6. Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebaek; Røder, Martin Andreas; Rathenborg, Per;

    2014-01-01

    OBJECTIVE: The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post-chemotherapy......%). Forty-six percent had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate with the number of prior cancer treatments (p = 0.57), time from diagnosis to mCRPC (p = 0.11) or prior response to docetaxel (p = 0.67). However, patients treated with second line cabazitaxel...... marked fall in PSA following enzalutamide therapy in post-chemotherapy mCRPC patients compared with reported results in randomized trials. Larger prospective studies of sequencing are warranted....

  7. The expression of receptors for estrogen and epithelial growth factor in the male rabbit prostate and prostatic urethra following castration

    DEFF Research Database (Denmark)

    Bødker, A; Balslev, E; Iversen, H G;

    1997-01-01

    In the lower urinary tract of the male rabbit, estrogen receptors (ERs) are restricted to the urethra and the prostatic stroma. At present, the function of ERs in these tissues is not known. Epithelial growth factor (EGF) stimulates proliferation of epidermal and epithelial tissues, and several...... were included as controls. In the control group, ERs were found in the urothelial lining and lamina propria of the prostatic urethra, and in the prostatic stroma. EGF receptors were demonstrated in the epithelial lining of the prostatic urethra and the glandular epithelium of the prostate. Following...... castration, the expression of ERs, assessed as the increase in the number of positively stained specimens, increased significantly in the lamina propria of the prostatic urethra and the prostatic stroma. EGF receptor expression increased significantly in the epithelial lining of the prostatic urethra. In the...

  8. Influence of hands-on experience on pig farmers' attitude towards alternatives for surgical castration of male piglets.

    Science.gov (United States)

    Aluwé, M; Vanhonacker, F; Millet, S; Tuyttens, A M

    2015-12-01

    This study evaluates the influence of practical experience with alternatives for surgical castration (SC) on farmer attitudes. Nineteen farmers in Flanders were surveyed before (ex-ante) and after (ex-post) performing each of five treatments on farm: 1) SC with analgesia (SCAN); 2) SC with CO2 anaesthesia (SCCO2); 3) immunocastration (IM); 4) production of entire males (EM); and 5) SC without pain relief (SCN). For SCCO2 and SCAN, farmers mainly experienced disadvantages in terms of increased labour, costs and complexity. Hands-on experience promoted EMas a valid alternative for SCN due to the actual and perceived improvement in performance and profitability as well as the reduced labour demands. Experience with IM did not fully fulfil the favourable ex-ante expectations resulting in a level of dissatisfaction and a less favourable general attitude ex-post.

  9. Parasitic castration by the digenian trematode Allopodocotyle sp. alters gene expression in the brain of the host mollusc Haliotis asinina.

    Science.gov (United States)

    Rice, Tamika; McGraw, Elizabeth; O'Brien, Elizabeth K; Reverter, Antonio; Jackson, Daniel J; Degnan, Bernard M

    2006-06-26

    Infection of molluscs by digenean trematode parasites typically results in the repression of reproduction -- the so-called parasitic castration. This is known to occur by altering the expression of a range of host neuropeptide genes. Here we analyse the expression levels of 10 members of POU, Pax, Sox and Hox transcription factor gene families, along with genes encoding FMRFamide, prohormone convertase and beta-tubulin, in the brain ganglia of actively reproducing (summer), non-reproducing (winter) and infected Haliotis asinina (a vetigastropod mollusc). A number of the regulatory genes are differentially expressed in parasitised H. asinina, but in only a few cases do expression patterns in infected animals match those occurring in animals where reproduction is normally repressed.

  10. Further analysis of PREVAIL: Enzalutamide use in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Jeanny B Aragon-Ching

    2014-12-01

    Full Text Available PREVAIL was a phase III multinational, double-blind, placebo-controlled trial that enrolled chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC, which showed remarkable improvement in co-primary endpoints with an overall 81% reduction in the risk of radiographic progression, as well as 29% reduction in the risk of death in favor of the enzalutamide arm over placebo. All secondary endpoints including time to subsequent chemotherapy initiation and prostate specific antigen (PSA progression were in favor of the enzalutamide arm. The results of PREVAIL shows the utility of enzalutamide that would likely soon expand the indication to asymptomatic or minimally symptomatic men with mCRPC not previously treated with chemotherapy.

  11. Targeting autophagy overcomes Enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model

    Science.gov (United States)

    Nguyen, H G; Yang, J C; Kung, H-J; Shi, X-B; Tilki, D; Lara, P N; DeVere White, R W; Gao, A C; Evans, C P

    2014-01-01

    Macro-autophagy is associated with drug resistance in various cancers and can function as an adaptive response to maintain cell survival under metabolic stresses, including androgen deprivation. Androgen deprivation or treatment with androgen receptor (AR) signaling inhibitor (ARSI), Enzalutamide (MDV-3100, ENZA) or bicalutamide induced autophagy in androgen-dependent and in castration-resistant CaP (castration-resistant prostate cancer (CRPC)) cell lines. The autophagic cascade triggered by AR blockage, correlated with the increased light chain 3-II/I ratio and ATG-5 expression. Autophagy was observed in a subpopulation of C4-2B cells that developed insensitivity to ENZA after sustained exposure in culture. Using flow cytometry and clonogenic assays, we showed that inhibiting autophagy with clomipramine (CMI), chloroquine or metformin increased apoptosis and significantly impaired cell viability. This autophagic process was mediated by AMP-dependent protein kinase (AMPK) activation and the suppression of mammalian target of rapamycin (mTOR) through Raptor phosphorylation (Serine 792). Furthermore, small interfering RNA targeting AMPK significantly inhibited autophagy and promoted cell death in CaP cells acutely or chronically exposed to ENZA or androgen deprivation, suggesting that autophagy is an important survival mechanism in CRPC. Lastly, in vivo studies with mice orthotopically implanted with ENZA-resistant cells demonstrated that the combination of ENZA and autophagy modulators, CMI or metformin significantly reduced tumor growth when compared with control groups (P<0.005). In conclusion, autophagy is as an important mechanism of resistance to ARSI in CRPC. Antiandrogen-induced autophagy is mediated through the activation of AMPK pathway and the suppression of mTOR pathway. Blocking autophagy pharmacologically or genetically significantly impairs prostate cancer cell survival in vitro and in vivo, implying the therapeutics potential of autophagy inhibitors

  12. Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer.

    Science.gov (United States)

    McGrath, Meagan J; Binge, Lauren C; Sriratana, Absorn; Wang, Hong; Robinson, Paul A; Pook, David; Fedele, Clare G; Brown, Susan; Dyson, Jennifer M; Cottle, Denny L; Cowling, Belinda S; Niranjan, Birunthi; Risbridger, Gail P; Mitchell, Christina A

    2013-08-15

    It is now clear that progression from localized prostate cancer to incurable castrate-resistant prostate cancer (CRPC) is driven by continued androgen receptor (AR), signaling independently of androgen. Thus, there remains a strong rationale to suppress AR activity as the single most important therapeutic goal in CRPC treatment. Although the expression of ligand-independent AR splice variants confers resistance to AR-targeted therapy and progression to lethal castrate-resistant cancer, the molecular regulators of AR activity in CRPC remain unclear, in particular those pathways that potentiate the function of mutant AR in CRPC. Here, we identify FHL2 as a novel coactivator of ligand-independent AR variants that are important in CRPC. We show that the nuclear localization of FHL2 and coactivation of the AR is driven by calpain cleavage of the cytoskeletal protein filamin, a pathway that shows differential activation in prostate epithelial versus prostate cancer cell lines. We further identify a novel FHL2-AR-filamin transcription complex, revealing how deregulation of this axis promotes the constitutive, ligand-independent activation of AR variants, which are present in CRPC. Critically, the calpain-cleaved filamin fragment and FHL2 are present in the nucleus only in CRPC and not benign prostate tissue or localized prostate cancer. Thus, our work provides mechanistic insight into the enhanced AR activation, most notably of the recently identified AR variants, including AR-V7 that drives CRPC progression. Furthermore, our results identify the first disease-specific mechanism for deregulation of FHL2 nuclear localization during cancer progression. These results offer general import beyond prostate cancer, given that nuclear FHL2 is characteristic of other human cancers where oncogenic transcription factors that drive disease are activated like the AR in prostate cancer.

  13. Radium-223 dichloride: illustrating the benefits of a multidisciplinary approach for patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Renzulli II JF

    2015-06-01

    Full Text Available Joseph F Renzulli II, Jennifer Collins, Anthony Mega Genitourinary Multidisciplinary Clinic, The Miriam Hospital, Providence, RI, USAAbstract: Improving options for patients with metastatic castration-resistant prostate cancer (mCRPC provide latitude in designing treatment plans that meet patients' medical needs and personal goals. The field's rapid evolution opens avenues for contributions by multiple medical specialties and requires considering more options to ensure that each patient receives the most appropriate care. A multidisciplinary clinic (MDC focusing on patients with cancers of the genitourinary tract demonstrates an efficient and cost-effective means of integrating the diverse professional knowledge and skills needed to develop an optimal patient treatment plan. As a guide to establishing an MDC for patients with mCRPC, this article describes the operation of the Genitourinary MDC at The Miriam Hospital in Providence, RI – specifically, the successful incorporation of radium-223 dichloride (radium-223 into the treatment algorithm for men with mCRPC and symptomatic bone metastases. Radium-223 is a new treatment that, unlike earlier radionuclide therapies, has shown a survival advantage in a large randomized phase 3 trial (ALSYMPCA. The overall survival benefit was comparable to that of newer immuno- and hormonal therapies in similar populations. Radium-223 treatment also delayed onset of symptomatic skeletal events. Both benefits were independent of prior docetaxel therapy or concurrent bisphosphonate use. In our clinic, radium-223 is used primarily to extend patient survival. Patient selection, patient management, and treatment sequencing are discussed here in the context of a multidisciplinary environment. Keywords: radium-223 dichloride, prostate cancer, castration-resistant prostate cancer, multidisciplinary clinic, best practices

  14. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Harrison MR

    2013-01-01

    Full Text Available Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J GeorgeDuke Cancer Institute, Durham, NC, USABackground: Radium-223 chloride (223Ra; Alpharadin is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153, 223Ra delivers a high quantity of energy per track length with short tissue penetration.Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile.Methods: Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.Conclusion: Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab, which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153, which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC. Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel

  15. Recherche d'un âge optimal de castration chez la race bovine Alur en système d'élevage extensif au Zaïre

    Directory of Open Access Journals (Sweden)

    Dibanzilua, M.

    1993-01-01

    Full Text Available Determination of the optimum age for castration by the Alur cattle breed under extensive production in Zaire. Considering a few difficultes which seem to hinder the popularization of the castration technique in the real environment of Ituri (North Eastern Zaire, the authors suggest the trend towards the reducing of the age margin regularly observed during the running of that operation. It appeared that the age between 3 and 5 months seems favourable for the popularizer as well as for the animal and the breeder regarding the operation, the stress and the meat quality. Considering the yields in butchery the carcass weights of castrated animals are nearly the same as those of non castrated ones.

  16. Pain, PSA flare, and bone scan response in a patient with metastatic castration-resistant prostate cancer treated with radium-223, a case report

    International Nuclear Information System (INIS)

    Radium-223 has been shown to improve overall survival in men with metastatic castration-resistant prostate cancer with symptomatic bone metastases. The bone scan response to radium-223 has only been described in one single center trial of 14 patients, none of whom achieved the outstanding bone scan response presented in the current case. In this case report, we describe a 75 year-old white man with extensively pre-treated metastatic castration-resistant prostate cancer and symptomatic bone metastases who experienced a flare in pain and prostate-specific antigen, followed by dramatic clinical (pain), biochemical (prostate-specific antigen), and imaging (bone scan) response. The flare phenomena and bone scan response we observed have not previously been described with radium-223. This case suggests that the degree and duration of bone scan response may be predictive of overall survival benefit

  17. Stromal remodelling is required for progressive involution of the rat ventral prostate after castration: identification of a matrix metalloproteinase-dependent apoptotic wave.

    Science.gov (United States)

    Bruni-Cardoso, A; Augusto, T M; Pravatta, H; Damas-Souza, D M; Carvalho, H F

    2010-10-01

    Prostate epithelial-cell apoptosis occurs in response to androgen deprivation. We have hypothesized that continued regression would require stromal changes. Studying apoptosis kinetics up to the 14th day after castration, we identified successive waves of apoptosis, with a prominent peak on day 11. This peak was associated with caspase-3 activity, nuclear translocation of apoptosis-inducing factor and clusterin expression. The apoptosis peak on day 11 was preceded by increased MMP-2 and MMP-7 activation, and MMP-9 expression on days 9 and 10. Treatment with the matrix metalloproteinases inhibitors doxycyclin, hydrocortisone, or GM6001 caused significant reduction in the apoptosis rate on day 11. The present data demonstrate that prostatic epithelial-cell deletion at the 11th day after castration was induced by focal degradation of the extracellular matrix associated with stromal remodelling. PMID:19906188

  18. Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor.

    Science.gov (United States)

    Patki, Mugdha; Huang, Yanfang; Ratnam, Manohar

    2016-07-22

    It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen-induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co-expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone-independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. PMID:27179779

  19. Differences in treatment patterns among patients with castration-resistant prostate cancer treated by oncologists versus urologists in a US managed care population

    OpenAIRE

    Alemayehu,

    2011-01-01

    Nicole M Engel-Nitz1, Berhanu Alemayehu2, David Parry3, Faith Nathan21Innovus, Eden Prairie, MN, USA; 2AstraZeneca, Wilmington, DE, USA; 3AstraZeneca UK, London, UKObjective: Differences in treatment patterns, health care resource utilization, and costs between patients with castration-resistant prostate cancer (CRPC) treated by oncologists and those treated by urologists were examined.Methods: Patients aged ≥40 with CRPC were identified using claims from a large US managed health care...

  20. A multi-centre randomised phase III trial of Dexamethasone vs Dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred Diethylstilbestrol

    OpenAIRE

    Shamash, J; Powles, T; Sarker, S J; Protheroe, A; Mithal, N; Mills, R.; Beard, R; Wilson, P; Tranter, N.; O'Brien, N; McFaul, S; Oliver, T

    2011-01-01

    Background: The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS). Methods: From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either D...

  1. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

    OpenAIRE

    Kim, Choung-Soo; Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-01-01

    Purpose This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-...

  2. Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone

    OpenAIRE

    De Giorgi, Ugo; Caroli, Paola; Burgio, Salvatore L.; Menna, Cecilia; Conteduca, Vincenza; Bianchi, Emanuela; Fabbri, Francesca; Carretta, Elisa; Amadori, Dino; Paganelli, Giovanni; Matteucci, Federica

    2014-01-01

    Objective: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC). Patient and methods: Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/C...

  3. Abiraterone acetate in patients with metastatic castration-resistant prostate cancer: long term outcome of the Temporary Authorization for Use programme in France

    OpenAIRE

    Houédé, Nadine; Beuzeboc, Philippe; Gourgou, Sophie; Tosi, Diego; Moise, Laura; Gravis, Gwenaëlle; Delva, Remy; Fléchon, Aude; Latorzeff, Igor; Ferrero, Jean-Marc; Oudard, Stéphane; Tartas, Sophie; Laguerre, Brigitte; Topart, Delphine; Roubaud, Guilhem

    2015-01-01

    AbstractBackgroundCOU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to eva...

  4. A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time

    OpenAIRE

    Noguchi, Masanori; MORIYA, FUKUKO; SUEKANE, SHIGETAKA; Ohnishi, Rei; Matsueda, Satoko; Sasada, Tetsuro; Yamada, Akira; Itoh, Kyogo

    2013-01-01

    Background Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are curren...

  5. Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells

    OpenAIRE

    Huang, E-Chu; Zhao, Yi; Chen, Guoxun; Baek, Seung Joon; McEntee, Michael F.; Minkin, Steven; Biggerstaff, John P.; Whelan, Jay

    2014-01-01

    Background Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer. The current experiments were designed to investigate the effects of Zyflamend on the expression of class I and II histone deacetylases, a family of enzymes known to be over expressed in a variety of cancers. Methods CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and I...

  6. Effects of immunological castration and distiller's dried grains with solubles on carcass cutability and commercial bacon slicing yields of barrows slaughtered at two time points.

    Science.gov (United States)

    Tavárez, M A; Bohrer, B M; Asmus, M D; Schroeder, A L; Matulis, R J; Boler, D D; Dilger, A C

    2014-07-01

    Male pigs were randomly assigned to a castration method at birth and allotted to 48 pens (28 pigs/pen). Physically castrated (PC) barrows were castrated at 2 d of age; immunologically castrated (IC) barrows were administered Improvest (GnRF analog diphtheria toxoid conjugate; Zoetis, Kalamazoo, MI) at 16 and 20 wk of age. Distiller's dried grains with solubles (DDGS) feeding strategies included either 0% DDGS (control), 30% DDGS (30% DDGS) fed from 6 wk of age to slaughter, or 30% DDGS fed from 6 wk of age to second dose of Improvest and then fed 0% DDGS until slaughter (withdrawal). Four barrows closest to the median pen weight at 4.5 wk after second dose were selected for evaluation; two were randomly selected and slaughtered at 5 wk and the other two at 7 wk after second dose. Data from each slaughter time were analyzed independently as a 2 × 3 factorial design with pen as the experimental unit. At 5 wk after second dose, bone-in lean cutting yields were 2.63% units greater (P green weight) were 6.10% units less (P lean cutting yields were 1.57% units greater (P = 0.03) in IC compared with PC. Distiller's grains feeding strategy had no effect (P ≥ 0.83) on boneless carcass cutting yields in IC; while in PC, these yields were 2.32% units less (P green weight) were 4.27% units less (P = 0.05) in IC compared with PC. These data suggested that while bacon slicing yield was reduced in IC barrows fed control and 30% DDGS compared with PC barrow counterparts, withdrawal of DDGS improved bacon slicing yields of IC barrows. PMID:24879762

  7. Mitosis Phase Enrichment with Identification of Mitotic Centromere-Associated Kinesin As a Therapeutic Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Liu, Yuexin; Dhillon, Jasreman; Cogdell, David; Aprikian, Armen; Efstathiou, Eleni; Navone, Nora; Troncoso, Patricia; Zhang, Wei

    2012-01-01

    The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason–grade hormone-sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy-resistant CRPC samples (n = 25) was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10) and hormone-sensitive prostate cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target. PMID:22363599

  8. Mitosis phase enrichment with identification of mitotic centromere-associated kinesin as a therapeutic target in castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kanishka Sircar

    Full Text Available The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason-grade hormone-sensitive prostate cancer (P<0.0001. Expression profiling of chemotherapy-resistant CRPC samples (n = 25 was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10 and hormone-sensitive prostate cancer cases (n = 108. Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target.

  9. Student Perceptions of the Use of a Laser Pointer for Intra-Operative Guidance in Feline Castration.

    Science.gov (United States)

    Badman, Märit; Höglund, Katja; Höglund, Odd V

    2016-01-01

    In veterinary clinical education, students perform surgery under guided supervision. This study aimed to determine if students' perception of how well they understood verbal guidance could be improved by using a laser pointer during feline castration. It was assumed that a teacher's use of a laser pointer could help students identify structures of importance during surgery. The hypothesis was that use of a laser pointer would improve student understanding of verbal guidance during surgery. Eighteen privately owned male cats were electively neutered by fourth- and fifth-year veterinary students at the Swedish University of Agricultural Sciences, Uppsala, Sweden. Each student performed orchiectomy on one cat. One testis was removed while the student received verbal guidance combined with a laser pointer, and the other testis was removed while the student received only verbal guidance. The use of a laser pointer alternated between first and second testis. After surgery, students rated how well they understood verbal guidance on a visual-analog scale (100 mm) for each instructional method. The two ratings were compared in a student's two-sided t-test. The median score with or without guidance with a laser pointer was 81 (59-96) and 54 (25-86), respectively (p<.001). This study showed that laser pointers enhanced verbal guidance given to students during surgery. The suggested mechanism of explanation is that the technology enabled a more precise guidance of location and identification of anatomic structures. PMID:27128854

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Early Prediction of Therapy Response to Abiraterone Acetate Using PSA Subforms in Patients with Castration Resistant Prostate Cancer.

    Science.gov (United States)

    Schlack, Katrin; Krabbe, Laura-Maria; Fobker, Manfred; Schrader, Andres Jan; Semjonow, Axel; Boegemann, Martin

    2016-01-01

    The purpose of this study was to evaluate the prognostic ability of early changes of total prostate specific antigen (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) following initiation of Abiraterone-therapy in men with castration resistant prostate cancer (mCRPC). In 25 patients, PSA-subforms were analyzed before and at 8-12 weeks under therapy as prognosticators of progression-free-survival (PFS) and overall survival (OS). Comparing patients with a PFS 15 months of OS there was a non-significant trend for a difference in the relative-median-change of fPSA (17.0% vs. -46.3%; p = 0.06). In Kaplan-Meier analyses, declining fPSA and [-2]proPSA were associated with a longer median PFS (13 months, 95% confidence interval (CI): 9.6-16.4 vs. 10 months, 95% CI: 3.5-16.5; p = 0.11), respectively. Correspondingly, decreasing fPSA and [-2]proPSA values indicated an OS of 32 months (95% CI: not reached (NR)) compared to 21 months in men with rising values (95% CI: 7.7-34.3; p = 0.14), respectively. We concluded that the addition of fPSA- and [-2]proPSA-changes to tPSA-information might be further studied as potential markers of early Abiraterone response in mCRPC patients. PMID:27618028

  12. Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

    Directory of Open Access Journals (Sweden)

    Mukherji D

    2014-05-01

    Full Text Available Deborah Mukherji,1 Imane El Dika,1 Sally Temraz,1 Mohammed Haidar,2 Ali Shamseddine11Department of Hematology/Oncology, 2Department of Nuclear Medicine, American University of Beirut Medical Center, Beirut, LebanonAbstract: Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical approved for the treatment of bone metastatic castration-resistant prostate cancer. Radium-223 is administered intravenously with no requirement for complex shielding and specifically targets areas of bone metastasis. In a randomized placebo-controlled Phase III study, treatment with radium-223 was shown to improve overall survival, time to skeletal-related events, and health-related quality of life. Apart from radium-223, the cytotoxic chemotherapy agents docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate, novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been shown to improve survival of men with advanced prostate cancer in Phase III trials. This review will outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 in changing treatment paradigms.Keywords: Alpharadin, alpha-emitting radionuclide, bone metastasis

  13. Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

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    A. V. Rudakova

    2014-01-01

    Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

  14. Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Peizhen Hu

    Full Text Available The potential application of multiplexed quantum dot labeling (MQDL for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL, at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity.

  15. Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer.

    Science.gov (United States)

    Hu, Peizhen; Chu, Gina C-Y; Zhu, Guodong; Yang, Hua; Luthringer, Daniel; Prins, Gail; Habib, Fouad; Wang, Yuzhuo; Wang, Ruoxiang; Chung, Leland W K; Zhau, Haiyen E

    2011-01-01

    The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity. PMID:22205960

  16. Efeito da tibolona sobre o endométrio de ratas castradas Effect of tibolone on endometrium of castrated rats

    Directory of Open Access Journals (Sweden)

    José Augusto Soares Pantaleão

    2009-03-01

    Full Text Available OBJETIVO: avaliar o efeito do uso prolongado de alta dose de tibolona na morfologia do endométrio em ratas castradas. MÉTODOS: foram utilizadas 15 ratas Wistar, fêmeas, com idade de oito semanas e peso médio de 250 g. Todas as ratas foram submetidas à ooforectomia bilateral e 30 dias depois foi coletada citologia vaginal, verificando-se o status de menopausa. As ratas foram divididas aleatoriamente em dois grupos: o tratado (n=9 recebeu via oral 1 mg tibolona/dia; o controle (n=6 recebeu apenas solução do veículo carboximetilcelulose. Após 20 semanas de tratamento, todos os animais foram sedados e sacrificados por deslocamento cervical. Os úteros foram retirados e fixados em formol 10% tamponado. Ambos os cornos uterinos foram clivados em três regiões (proximal, medial, distal e processados para inclusão em parafina. Cortes histológicos corados com hematoxilina-eosina foram submetidos à análise morfológica e morfométrica. Foram avaliados os seguintes parâmetros: espessura do epitélio superficial endometrial, espessura do estroma endometrial, área endometrial, número absoluto de glândulas endometriais e número de glândulas/área endometrial. Os dados obtidos foram comparados mediante o teste t de Student. RESULTADOS: no Grupo Tibolona os úteros se apresentaram bem desenvolvidos e houve aumento significativo (pPURPOSE: to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometrium of castrated female rats. METHODS: fifteen female Wistar rats, aged eight weeks and weighting about 250 g were used. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9 received 1 mg of tibolone/day orally; the Control Group (n=6 received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were

  17. MOR209/ES414, a Novel Bispecific Antibody Targeting PSMA for the Treatment of Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Hernandez-Hoyos, Gabriela; Sewell, Toddy; Bader, Robert; Bannink, Jeannette; Chenault, Ruth A; Daugherty, Mollie; Dasovich, Maria; Fang, Hang; Gottschalk, Rebecca; Kumer, John; Miller, Robert E; Ravikumar, Padma; Wiens, Jennifer; Algate, Paul A; Bienvenue, David; McMahan, Catherine J; Natarajan, Sateesh K; Gross, Jane A; Blankenship, John W

    2016-09-01

    Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains a highly unmet medical need and current therapies ultimately result in disease progression. Immunotherapy is a rapidly growing approach for treatment of cancer but has shown limited success to date in the treatment of mCRPC. We have developed a novel humanized bispecific antibody, MOR209/ES414, built on the ADAPTIR (modular protein technology) platform, to redirect T-cell cytotoxicity toward prostate cancer cells by specifically targeting T cells through CD3ε to prostate cancer cells expressing PSMA (prostate-specific membrane antigen). In vitro cross-linking of T cells with PSMA-expressing tumor cells by MOR209/ES414 triggered potent target-dependent tumor lysis and induction of target-dependent T-cell activation and proliferation. This activity occurred at low picomolar concentrations of MOR209/ES414 and was effective at low T-effector to tumor target cell ratios. In addition, cytotoxic activity was equivalent over a wide range of PSMA expression on target cells, suggesting that as few as 3,700 PSMA receptors per cell are sufficient for tumor lysis. In addition to high sensitivity and in vitro activity, MOR209/ES414 induced limited production of cytokines compared with other bispecific antibody formats. Pharmacokinetic analysis of MOR209/ES414 demonstrated a serum elimination half-life in NOD/SCID γ (NSG) mice of 4 days. Administration of MOR209/ES414 in murine xenograft models of human prostate cancer significantly inhibited tumor growth, prolonged survival, and decreased serum prostate-specific antigen levels only in the presence of adoptively transferred human T cells. On the basis of these preclinical findings, MOR209/ES414 warrants further investigation as a potential therapeutic for the treatment of CRPC. Mol Cancer Ther; 15(9); 2155-65. ©2016 AACR. PMID:27406985

  18. Hypoxic tumor kinase signaling mediated by STAT5A in development of castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kathrine Røe

    Full Text Available In this study, we hypothesized that androgen-deprivation therapy (ADT in prostate cancer, although initially efficient, induces changes in the tumor kinome, which subsequently promote development of castration-resistant (CR disease. Recognizing the correlation between tumor hypoxia and poor prognosis in prostate cancer, we further hypothesized that such changes might be influenced by hypoxia. Microarrays with 144 kinase peptide substrates were applied to analyze CWR22 prostate carcinoma xenograft samples from ADT-naïve, androgen-deprived (AD, long-term AD (ADL, and CR disease stages. The impact of hypoxia was assessed by matching the xenograft kinase activity profiles with those acquired from hypoxic and normoxic prostate carcinoma cell cultures, whereas the clinical relevance was evaluated by analyzing prostatectomy tumor samples from patients with locally advanced disease, either in ADT-naïve or early CR disease stages. By using this novel peptide substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A in CR prostate cancer. Additionally, we uncovered high STAT5A kinase activity already in regressing ADL xenografts, before renewed CR growth was evidenced. Finally, since increased STAT5A kinase activity also was detected after exposing prostate carcinoma cells to hypoxia, we propose long-term ADT to induce tumor hypoxia and stimulate STAT5A kinase activity, subsequently leading to renewed CR tumor growth. Hence, the study detected STAT5A as a candidate to be further investigated for its potential as marker of advanced prostate cancer and as possible therapeutic target protein.

  19. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perk, T; Bradshaw, T; Harmon, S; Perlman, S; Liu, G; Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2015-06-15

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation.

  20. The use of circulating tumor cells in guiding treatment decisions for patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Onstenk, Wendy; de Klaver, Willemijn; de Wit, Ronald; Lolkema, Martijn; Foekens, John; Sleijfer, Stefan

    2016-05-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has drastically changed over the past decade with the advent of several new anti-tumor agents. Oncologists increasingly face dilemmas concerning the best treatment sequence for individual patients since most of the novel compounds have been investigated and subsequently positioned either pre- or post-docetaxel. A currently unmet need exists for biomarkers able to guide treatment decisions and to capture treatment resistance at an early stage thereby allowing for an early change to an alternative strategy. Circulating tumor cells (CTCs) have in this context intensively been investigated over the last years. The CTC count, as determined by the CellSearch System (Janssen Diagnostics LLC, Raritan, NJ), is a strong, independent prognostic factor for overall survival in patients with mCRPC at various time points during treatment and, as an early response marker, outperforms traditional response evaluations using serum prostate specific antigen (PSA) levels, scintigraphy as well as radiography. The focus of research is now shifting toward the predictive value of CTCs and the use of the characterization of CTCs to guide the selection of treatments with the highest chance of success for individual patients. Recently, the presence of the androgen receptor splice variant 7 (AR-V7) has been shown to be a promising predictive factor. In this review, we have explored the clinical value of the enumeration and characterization of CTCs for the treatment of mCRPC and have put the results obtained from recent studies investigating the prognostic and predictive value of CTCs into clinical perspective. PMID:27107266

  1. Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis.

    Directory of Open Access Journals (Sweden)

    Lixian Zhong

    Full Text Available BACKGROUND: Docetaxel is an established first-line therapy to treat metastatic castration-resistant prostate cancer (mCRPC. Recently, abiraterone and cabazitaxel were approved for use after docetaxel failure, with improved survival. National Institute for Health and Clinical Excellence (NICE preliminary recommendations were negative for both abiraterone (now positive in final recommendation and cabazitaxel (negative in final recommendation. OBJECTIVE: To evaluate the cost-effectiveness of abiraterone, cabazitaxel, mitoxantrone and prednisone for mCRPC treatment in US. METHODS: A decision-tree model was constructed to compare the two mCRPC treatments versus two placebos over 18 months from a societal perspective. Chance nodes include baseline pain as a severity indicator, grade III/IV side-effects, and survival at 18 months. Probabilities, survival and health utilities were from published studies. Model cost inputs included drug treatment, side-effect management and prevention, radiation for pain, and death associated costs in 2010 US dollars. RESULTS: Abiraterone is a cost-effective choice at $94K/QALY (quality adjusted life years compared to placebo in our base-case analysis. Cabazitaxel and abiraterone are the most effective, yet also most expensive agents. The incremental cost-effectiveness ratios (ICER at base-case are $101K/QALY (extended dominated for mitoxantrone vs. placebo, $91K/QALY for abiraterone vs. mitoxantrone, $956K/QALY for cabazitaxel vs. abiraterone. Abiraterone becomes less cost-effective as its AWP increases, or if the cost of mitoxantrone side-effect management decreases. Increases in the percentage of patients with baseline pain leads to an increased ICER for both mitoxantrone and abiraterone, but mitoxantrone does relatively better. Cabazitaxel remains not cost-effective. CONCLUSION: Our base case model suggests that abiraterone is a cost-effective option in docetaxel-refractory mCRPC patients. Newer treatments will also

  2. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation

  3. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    International Nuclear Information System (INIS)

    Radium-223 chloride (223Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), 223Ra delivers a high quantity of energy per track length with short tissue penetration. This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile. Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database. Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents

  4. Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

    Directory of Open Access Journals (Sweden)

    Jeremy YC Teoh

    2015-06-01

    Full Text Available We investigated the cardiovascular thrombotic risk after surgical castration (SC versus gonadotropin-releasing hormone agonists (GnRHa in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years was significantly higher than the GnRHa group (71.8 ± 8.3 years (P < 0.001. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P = 0.014. Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P< 0.001, hyperlipidemia (HR 2.455, 95% CI 1.53-3.93, P< 0.001, and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031 were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

  5. TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

    Directory of Open Access Journals (Sweden)

    Orla M Casey

    Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

  6. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    Science.gov (United States)

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) cancer-specific survival and biochemical progression remained unclear. Non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. PMID:25523493

  7. Lipid oxidation, sensory characteristics, and color of fresh pork sausage from immunologically castrated pigs stored frozen for up to 12 weeks.

    Science.gov (United States)

    Jones-Hamlow, Katelyn A; Tavárez, Marcos A; Schroeder, Aubrey L; Dilger, Anna C

    2016-05-01

    Two studies were conducted to evaluate the quality characteristics of fresh sausage manufactured from immunologically castrated (IC) pigs, an emerging technology in the pork industry. Study 1: Fresh sausage patties from ground Boston butts fabricated from PC (physically castrated) pigs fed 0.55% SID (standard illeal digestible) lysine, IC pigs fed 0.55% SID lysine, and IC pigs fed 0.65% SID lysine were made and not standardized to a similar content of fat content. Study 2: fat and lean trim obtained from IC and PC pigs was made into fresh sausage patties, targeting 25% lipid. Patties (1.25 cm) were placed on trays and assigned to 0, 4, or 12 weeks frozen storage and then, after frozen storage, placed in simulated retail display conditions for 5 days. Patties were evaluated for color stability, sensory and textural properties, and lipid oxidation. Data were analyzed as a one way ANOVA with repeated measures where appropriate. In both studies, sausage discolored with both increased time in frozen storage and with increased time in retail display (P < 0.01). However, within each week of frozen storage, all treatments were equally discolored in both studies. Treatment did not affect the sensory characteristics or textural properties of fresh sausage in either study. Lipid oxidation did not differ by treatment in study 1. In study 2, lipid oxidation was reduced (P < 0.05) in IC compared to PC by approximately 0.1 mg malonaldehyde/kg meat, but there were no differences within each storage week. Increasing frozen storage time increased lipid oxidation an off-flavor scores in both studies (P < 0.05). Overall, immunological castration had no detrimental effects on color stability, sensory characteristics, or textural properties of fresh pork sausage. PMID:27247765

  8. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Evans, Christopher P; Higano, Celestia S; Keane, Thomas;

    2016-01-01

    BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. OBJECTIVE: To assess the...... while continuing androgen deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. RESULTS AND LIMITATIONS: Enzalutamide improved rPFS versus placebo...... significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. PATIENT SUMMARY: Patients with metastatic castration-resistant prostate cancer-including those with or without...

  9. Castration du porcelet : évaluation de l'efficacité analgésique per-opératoire de l'huile essentielle Mentha arvensis (menthe des champs) par l'analyse des vocalisations

    OpenAIRE

    Zbik, Marion

    2013-01-01

    La castration des porcelets mâles est légalement pratiquée avant l'âge de 7 jours sans analgésie ni anesthésie, Cette castration chirurgicale cause une douleur importante aux porcelets. Dans un contexte où le bien-être animal a une place importante, et où l'engouement pour les "médecines alternatives" prend de l'ampleur, l'objet de notre projet est d'évaluer l'efficacité analgésique de l'huile essentielle de menthe des champs en application topique avant la castration, L'outil choisi pour éva...

  10. The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

    OpenAIRE

    Bian, Xiao-Jie; Zhu, Yao; Shen, Yi-Jun; Wang, Jin-You; Ma, Chun-Guang; Zhang, Hai-Liang; Dai, Bo; Zhang, Shi-Lin; Yao, Xu-Dong; Ye, Ding-Wei

    2013-01-01

    Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer (mCRPC) after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy (docetaxel or ...

  11. A Multicenter, Randomized Clinical Trial Comparing the Three-Weekly Docetaxel Regimen plus Prednisone versus Mitoxantone plus Prednisone for Chinese Patients with Metastatic Castration Refractory Prostate Cancer

    OpenAIRE

    Tie Zhou; Shu-xiong Zeng; Ding-wei Ye; Qiang Wei; Xu Zhang; Yi-ran Huang; Zhang-qun Ye; Yong Yang; , Wei Zhang; Ye Tian; Fang-jian Zhou; Jin Jie; Shi-ping Chen; Yan Sun; Li-ping Xie

    2015-01-01

    Purpose To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC). Patients and methods A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Pr...

  12. Field experience with surgical castration with anaesthesia, analgesia, immunocastration and production of entire male pigs: performance, carcass traits and boar taint prevalence.

    Science.gov (United States)

    Aluwé, M; Tuyttens, F A M; Millet, S

    2015-03-01

    Male piglets are castrated to reduce boar taint and also to reduce aggressive and sexual behaviour. However, the procedure as traditionally performed is painful and negatively affects performance. Large-scale results about the consequences of implementing alternatives on farms are lacking. We, therefore, investigated the practical applicability of the following five alternatives that can be implemented in the short term: surgical castration (1) without pain relief (CONT, control group), (2) with analgesia (MET, Metacam, 0.2 ml, 10 to 15 min before castration), (3) with general anaesthesia (CO2, inhalation, 100% CO2, 25 s, 3 l/min), (4) vaccination against boar taint (IM, two injections with Improvac) and (5) production of entire males (EM). The study consisted of the following two trials: (1) an experimental farm trial with 18 animals/treatment and (2) a large field trial on 20 farms with ~120 male pigs/farm per treatment and all treatments performed on each farm. Performance results as well as data on carcass traits, boar taint (hot-iron method) and testes development and weight were collected in both trials. Neither castration nor administration of analgesia or anaesthesia had an effect on daily gain of the piglets in the farrowing crates (P>0.05). Farmer records indicated that mortality in the farrowing crates (1.1%), nursery pens (1.8%) and fattening stable (2.2%) was not influenced by MET or CO2 compared with EM, IM or CONT (P>0.05). No significant differences were found for daily gain (P>0.05) nor slaughter age (P>0.05). Immunocastrates and EM had a better gain-to-feed ratio (P<0.05) compared with the groups of barrows (CONT, MET and CO2). Lean meat percentage was higher for EM compared with the barrows, and intermediate for IM (P<0.05). Carcass yield was lowest for IM (P<0.05). The hot-iron method indicated that boar taint was eliminated in barrows and IM compared with EM (P<0.001). Average prevalence of strong boar taint was 3% for EM, but varied from 0% to

  13. Ganho de peso e componentes do peso vivo em borregos Ile de France inteiros ou castrados e Hampshire Down castrados abatidos aos doze meses de idade Weight gain and live weight components of intact or castrated Ile de France and castrated Hampshire Down lambs slaughtered at twelve months of age

    Directory of Open Access Journals (Sweden)

    Edson Luis De Azambuja Ribeiro

    2000-04-01

    Full Text Available O principal objetivo deste trabalho foi o de avaliar o ganho de peso e os componentes do peso vivo em ovinos inteiros ou castrados abatidos aos 12 meses de idade. Foram usados 16 borregos Ile de France, sendo metade inteiros e metade castrados, e oito Hampshire Down castrados. Os borregos foram mantidos em pastagem de grama Coast-Cross e foram pesados dos três aos 12 meses de idade, quando abatidos. Não houve diferenças entre as raças para peso, ganhos de peso e para os componentes do peso vivo. Porém, os machos inteiros da raça Ile de France ganharam mais peso dos três aos 12 meses do que os castrados, com médias, respectivamente, de 0,078 e 0,063kg por dia; o ganho de peso médio diário para os borregos Hampshire Down foi de 0,064kg. As médias para os pesos vivos no abate e para os rendimentos de carcaça quente (entre parenteses foram: 38,54 (47,51%; 36,08 (47,82% e 36,44 (46,38%kg, respectivamente, para os borregos Ile de France inteiros, Ile de France castrados e Hampshire Down castrados. Os resultados indicam que, quando o abate for realizado aos 12 meses de idade, o uso de machos inteiros é recomendado devido ao seu maior ganho de peso.The main objective of this work was to evaluate the weight gain and live weight components of intact or castrated lambs slaughtered at 12 months of age. Sixteen Ile de France lambs, half intact and half castrated, and eight castrated Hampshire Down lambs were used in this experiment. The animals were kept on a Coast-Cross pasture from three to 12 months of age, and then slaughtered. There were no differences between breeds for weight, weight gain and live weight components. However, intact Ile de France lambs had a greater daily weight gain than castrated Ile de France lambs, with averages of 0.078 and 0.063kg, respectively; the average daily weight gain for the castrated Hampshire Down was 0.064kg. The averages for live weight before slaughtering and hot dressing percentage were: 38.54, 36

  14. Cytoarchitecture of steroid dependent target tissues after testosterone administration compared to nandrolone decanoate in castrated rats in the aim of Hershberger bio test.

    Science.gov (United States)

    Cristina, Romeo Teodor; Hanganu, Flavia; Brezovan, Diana; Dumitrescu, Eugenia; Muselin, Florin; Chiurciu, Viorica; Stancu, Adrian Constantin; Pentea, Marius Cristian; Motoc, Andrei Gheorghe Marius

    2014-01-01

    The objective was the cytoarchitecture evaluation of known steroid dependent target tissues after administering of testosterone, compared to action of its more active ester, nortestosterone (nandrolone decanoate) in castrated rat males in the aim of Hershberger bio test. Study was performed on 30 castrated male Wistar rats, aged between 35 and 39 days, in peripubertal period, divided into five groups. Androgen doses administration begun at the rats' age of 49 days. Animals were injected i.m., daily, for 10 consecutive days as follows: Aquatest (Balkan Pharmaceuticals Ltd., Moldova) testosterone aqueous solution: Testosterone I group (0.4 mg/animal); Testosterone II (0.8 mg/animal); (Deca-Durabolin, Balkan Pharmaceuticals); nandrolone decanoate oily solution: Nortestosterone I (1.5 mg/kg body weight); Nortestosterone II (7.5 mg/kg body weight) and Control (White sesame oil, Manicos, Romania, 0.1 mL/animal). Gonadectomy (GDX) induced modifications of target tissues wet weight accompanied by important modifications in cytoarchitecture. Changes following exogenous administration of testosterone and nortestosterone decanoate were found in: liver (granular dystrophy, mega-mitochondria, tubular intumescences), prostate (increasing of the structural elements), seminal vesicles (hyalinosis, thickening of cell walls and the hyaline presence), levator ani-bulbo-cavernosus muscle (muscle fibbers dilacerations), bulbourethral glands (muscular fibbers rarefaction by fluid accumulation) demonstrating the disruptor activity especially for overdosed nandrolone decanoate. PMID:25607397

  15. Lipid oxidation, sensory characteristics, and color of fresh pork sausage from immunologically castrated pigs stored frozen for up to 12 weeks.

    Science.gov (United States)

    Jones-Hamlow, Katelyn A; Tavárez, Marcos A; Schroeder, Aubrey L; Dilger, Anna C

    2016-05-01

    Two studies were conducted to evaluate the quality characteristics of fresh sausage manufactured from immunologically castrated (IC) pigs, an emerging technology in the pork industry. Study 1: Fresh sausage patties from ground Boston butts fabricated from PC (physically castrated) pigs fed 0.55% SID (standard illeal digestible) lysine, IC pigs fed 0.55% SID lysine, and IC pigs fed 0.65% SID lysine were made and not standardized to a similar content of fat content. Study 2: fat and lean trim obtained from IC and PC pigs was made into fresh sausage patties, targeting 25% lipid. Patties (1.25 cm) were placed on trays and assigned to 0, 4, or 12 weeks frozen storage and then, after frozen storage, placed in simulated retail display conditions for 5 days. Patties were evaluated for color stability, sensory and textural properties, and lipid oxidation. Data were analyzed as a one way ANOVA with repeated measures where appropriate. In both studies, sausage discolored with both increased time in frozen storage and with increased time in retail display (P sausage in either study. Lipid oxidation did not differ by treatment in study 1. In study 2, lipid oxidation was reduced (P sausage.

  16. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maryam Ghotbaddini

    2015-07-01

    Full Text Available The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR. TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models.

  17. Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Shen, Yuan-Chi; Chiang, Po-Hui; Luo, Hao-Lun; Chuang, Yao-Chi; Chen, Yen-Ta; Kang, Chih-Hsiung; Hsu, Chun-Chien; Lee, Wei-Ching; Cheng, Yuan-Tso

    2016-09-01

    To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3-12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects. PMID:27638405

  18. Effect of castration on the susceptibility of male rats to the sleep deprivation-induced impairment of behavioral and synaptic plasticity.

    Science.gov (United States)

    Hajali, Vahid; Sheibani, Vahid; Ghazvini, Hamed; Ghadiri, Tahereh; Valizadeh, Toktam; Saadati, Hakimeh; Shabani, Mohammad

    2015-09-01

    In both human and animal studies, the effect of sleep deficiency on cognitive performances has mostly been studied during adulthood in males, but very little data exist concerning the effects of poor sleep in gonadal hormones-depleted status, such as aging or gonadectomized (GDX) male animal models. The present study investigated the potential modulatory effects of the endogenous male sex hormones on the 48h REM sleep deprivation (SD)-induced cognitive and synaptic impairments by comparing the gonadally intact with castrated male rats, a rodent model of androgen-deprived male animals. The multiple platform method was used for inducing REM-SD and spatial performances were evaluated using Morris water maze (MWM) task. Early long-term potentiation (E-LTP) was measured in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess brain derived neurotrophic factor (BDNF) gene and protein expression in the hippocampus. To reveal any influence of sleep loss on stress level, we also evaluated the plasma corticosterone levels of animals. Regardless of reproductive status, REM-SD significantly disrupted short-term memory and LTP, as well as hippocampal BDNF expression. The corticosterone levels were not significantly changed following REM-SD neither in intact nor in GDX male rats. These findings suggest that depletion of male sex steroid hormones by castration does not lead to any heightened sensitivity of male animals to the deleterious effects of 48h REM-SD on cognitive and synaptic performances.

  19. Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT

    Directory of Open Access Journals (Sweden)

    Kalevi Kairemo

    2015-10-01

    Full Text Available The purpose of this study was to evaluate the outcome after Radium-223-dichloride (223RaCl2 treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body 18F-Fluoride PET/CT. Sodium 18F-fluoride [18F]-NaF PET/CT was performed prior the treatment of 223RaCl2, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [18F]-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [18F]-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during 223RaCl2. Our results (although preliminary suggest that 18F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases.

  20. {sup 11}C-Choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, UO Medicina Nucleare PAD. 30, Bologna (Italy); Castellucci, Paolo; Graziani, Tiziano; Renzi, Riccardo; Fanti, Stefano [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Schiavina, Riccardo; Borghesi, Marco; Brunocilla, Eugenio [University of Bologna, Department of Urology, S. Orsola-Malpighi Hospital, Bologna (Italy); Di Tullio, Piergiorgio; Ardizzoni, Andrea [University of Bologna, Department of Oncology, S. Orsola-Malpighi Hospital, Bologna (Italy)

    2016-01-15

    To investigate the role of {sup 11}C-choline PET/CT for evaluating the response to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel in comparison with PSA response. Inclusion criteria were (a) proven mCRPC, (b) docetaxel as first line of chemotherapy (docetaxel 75 mg/m{sup 2} + prednisone 5 mg), and (c) {sup 11}C-choline PET/CT and PSA values assessed before and after docetaxel administration. A total of 61 patients were retrospectively enrolled (mean age 68.9 years, range 57 - 84 years). {sup 11}C-Choline PET/CT was performed at baseline before docetaxel treatment (PET1) and after the end of treatment (PET2). PSA values were measured before treatment (PSA1) and after treatment (PSA2). PET2 was reported as complete response (CR), partial response (PR) or stable disease (SD). Progressive disease (PD) was considered if a new lesion was seen. PSA trend was calculated from the change in absolute values between PSA1 and PSA2. A decrease of ≥50 % between PSA1 and PSA2 was considered a PSA response. Clinical, radiological and laboratory follow-up ranged from 6 to 53 months (mean 13.5 months). Of the 61 patients, 40 (65.5 %) showed PD on PET2, 13 (21.3 %) showed SD, 2 (3.4 %) showed PR, and 6 (9.8 %) showed CR. An increasing PSA trend was seen in 29 patients (47.5 %) and a decreasing PSA trend in 32 patients (52.5 %). A PSA response of ≥50 % was seen in 25 patients (41 %). Radiological PD was seen in 23 of the 29 patients (79.3 %) with an increasing PSA trend, in 16 of the 32 patients (50 %) with a decreasing PSA trend, and in 11 of the 25 patients (44 %) with a PSA response of ≥50 %. In the multivariate statistical analysis, the presence of more than ten bone lesions detected on PET1 was significantly associated with an increased probability of PD on PET2. No association was observed between PSA level and PD on PET2. Our results suggest that an increasing PSA trend measured after docetaxel treatment could be

  1. Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo

    Science.gov (United States)

    Zhao, Jing; Liu, Juan; Wei, Tuo; Ma, Xiaowei; Cheng, Qiang; Huo, Shuaidong; Zhang, Chunqiu; Zhang, Yanan; Duan, Xianglin; Liang, Xing-Jie

    2016-02-01

    Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration-resistant prostate cancer'' (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL-1, which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 μM) of M-QCTs was much lower than free QCT (>200 μM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment.Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration

  2. Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo

    Science.gov (United States)

    Zhao, Jing; Liu, Juan; Wei, Tuo; Ma, Xiaowei; Cheng, Qiang; Huo, Shuaidong; Zhang, Chunqiu; Zhang, Yanan; Duan, Xianglin; Liang, Xing-Jie

    2016-02-01

    Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration-resistant prostate cancer'' (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL-1, which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 μM) of M-QCTs was much lower than free QCT (>200 μM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment.Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration

  3. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Fizazi, K.; Saad, F.; Mulders, P.F.A.; Sternberg, C.N.; Miller, K.; Logothetis, C.J.; Shore, N.D.; Small, E.J.; Carles, J.; Flaig, T.W.; Taplin, M.E.; Higano, C.S.; Souza, P. de; Bono, J.S. de; Griffin, T.W.; Porre, P. De; Yu, M.K.; Park, Y.C.; Li, J.; Kheoh, T.; Naini, V.; Molina, A.; Rathkopf, D.E.; Gerritsen, W.R.

    2015-01-01

    BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified f

  4. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I;

    2014-01-01

    BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel c...... that warrant further investigation. FUNDING: Bristol-Myers Squibb....

  5. Componentes não-integrantes da carcaça de novilhos não-castrados ou castrados terminados em confinamento e abatidos aos 16 ou 26 meses de idade Non-carcass components of castrate and non-castrated cattle finished in feedlot and slaughtered at 16 or 26 months of age

    Directory of Open Access Journals (Sweden)

    Fernando Kuss

    2008-10-01

    Full Text Available Foram avaliados os componentes não-integrantes da carcaça de novilhos terminados em confinamento e abatidos aos 16 (superjovem ou 26 (jovem meses de idade. A dieta foi formulada com 50% de volumoso e 50% de concentrado e continha 11,8% de proteína bruta e 2,83 Mcal de energia digestível por kg de matéria seca. Animais superjovens apresentaram maior rendimento de corpo vazio (92,39 versus 89,76% para os jovens, como resultado de seu menor conteúdo gastrintestinal (35,23 versus 53,46 kg para os jovens. Animais não-castrados apresentaram maior peso de cabeça (13,84 versus 12,35 kg, patas (11,12 versus 8,96 kg e couro (46,44 versus 37,71 kg em comparação aos castrados, o que está relacionado ao seu maior peso corporal (541,26 versus 445,47 kg. Observou-se influência da interação categoria x condição sexual sobre o peso absoluto dos órgãos vitais (coração, fígado e pulmões e dos componentes do trato gastrintestinal. O peso total de órgãos vitais e do trato gastrintestinal foi maior nos animais não-castrados, mas deixou de ser significativo quando ajustado para peso de corpo vazio (PCV e de abate (PA. Animais superjovens apresentaram maior peso absoluto das gorduras interna (25,91 versus 20,13 kg e de toalete (13,96 versus 10,98 kg. A castração dos animais resultou em maior participação de gordura interna calculada em relação ao peso de corpo vazio e ao peso de abate.The non-carcass components of castrated and non-castrated cattle (sex condition finished in feedlot and slaughtered at 16 (super young or 26 (young months of age (animal category were evaluated. The diet was formulated to contain 11.8% of CP and 2.83 Mcal/kg DM of DE with 50:50 forage to concentrate ratio (%MS. Super young animals showed higher of empty body dressing percentage (92.39 versus 89.76%, as a result of their lower gastrointestinal content (35.23 versus 53.46 kg as compared to the young animals. Non-castrate animals showed higher head weight (13

  6. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    Science.gov (United States)

    Satoh, Takefumi; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a ≥50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. Results Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by ≥1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (>20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. Conclusions Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical

  7. A Phase 2 Trial of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer and without Prior Chemotherapy (JPN-201 Study)

    Science.gov (United States)

    Matsubara, Nobuaki; Uemura, Hirotsugu; Satoh, Takefumi; Suzuki, Hiroyoshi; Nishiyama, Tsutomu; Uemura, Hiroji; Hashine, Katsuyoshi; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. Results A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: −66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2. Conclusions Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate

  8. Parasitic castration, growth, and sex steroids in the freshwater bonefish Cyphocharax gilbert (Curimatidae infested by Riggia paranensis (Cymothoidea

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    Neuza R. W. Lima

    2007-12-01

    Full Text Available Cyphocharax gilbert shows parasitic castration when infested by the crustacean Riggia paranensis, being unable to reproduce. Fish were sampled in the middle rio Itabapoana, Brazil, to study the prevalence of parasitism, growth, and sex steroid concentrations, considering the body size, sex, and reproductive condition of specimens. Most of the fish analyzed were infested (56.0%. The presence of two lines on the scales was more frequent among infested fish (22.0% than among fish without parasites (12.0% for females and 10.0% for males. The occurrence of three lines on the scales was rare (3.5% among infested and 2.0% among females without parasites. These results suggest that growth of the host is faster than that of non infested fish. The serum concentrations of sex steroids from fish without parasites varied at different gonadal development stages (17 beta-estradiol: 60.0 to 976.7 pg/ml; total testosterone: 220.0 to 3,887.7 pg/ml. All infested fish had lower levels of the two sex steroids and undeveloped gonads. Sex steroids levels in infested females were close to those in females at post-spawning stages. Total testosterone concentrations of infested males were below those of males at early gonadal maturation stage. These results suggest that R. paranensis reduces the reproductive capacity of C. gilbert by affecting the host endocrine system.Cyphocharax gilbert exibe castração parasitária quando está infestado pelo crustáceo Riggia paranensis, estando impossibilitado de reproduzir. Os peixes foram coletados no trecho médio do rio Itabapoana, Brasil, para analisar a prevalência do parasitismo, quantificar crescimento e as concentrações de esteróides sexuais, considerando o tamanho do corpo, o sexo e a condição reprodutiva dos espécimes. A maioria dos peixes analisados estava infestada (56,0%. A presença de duas linhas em escamas foi mais freqüente entre os peixes infestados (22,0% que entre os peixes não infestados (12,0% para as

  9. Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

    Science.gov (United States)

    Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

    2016-02-01

    We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy.

  10. Reflections on the therapeutic use of 223RaCl2 for bone metastases resulting from prostate cancer resistant to castration

    International Nuclear Information System (INIS)

    In January 2014 the Comision Federal para la Proteccion contra Riesgos Sanitarios of the Ministry of Health in Mexico, authorize the use of 223RaCl2 as the first radiopharmaceutical emitter α for therapeutic purposes in cases of bone metastases resulting from prostate cancer resistant to castration. The paper analyzes the main variables that affect the metrological traceability using activity meters to evaluate the gamma activity of 223RaCl2 in hospitals, because it has a chain of complex decay with alpha, beta and gamma emitters, so was important to verify if a gamma activity measurement for a multiple emitter is reliable to determine the total alpha absorbed dose to bone in a patient. (Author)

  11. Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide

    DEFF Research Database (Denmark)

    Anand, Aseem; Morris, Michael J; Larson, Steven M;

    2016-01-01

    BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength......-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall...... = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change...

  12. The evolution of cervical mucus infrastructure in normal cyclic baboons (Papio anubis) and castrated females receiving hormonal supplies. A scanning electron microscope study.

    Science.gov (United States)

    Chrétien, F C

    1980-01-01

    The scanning electron microscope was used to study the evolution of the infrastructure of cervical mucus in normal cyclic baboons and in castrated animals treated with ovarian hormones for establishing an artificial cycle. In both groups, the results make conspicuous the progressive enlargement of the filamentous woof, which attains a maximum at midcycle and then decreases by degrees in the second part of the cycle. It was shown that the evolution of the framework is very similar during normal and artificial cycle, with only variations of slight amplitude. Moreover, the variations in the baboon mucus infrastructure closely resemble those described in the human. The results are briefly discussed in the light of known data. PMID:6770577

  13. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.

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    Cai, Changmeng; Chen, Sen; Ng, Patrick; Bubley, Glenn J; Nelson, Peter S; Mostaghel, Elahe A; Marck, Brett; Matsumoto, Alvin M; Simon, Nicholas I; Wang, Hongyun; Chen, Shaoyong; Balk, Steven P

    2011-10-15

    Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.

  14. 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...... in secondary endpoints were observed. CONCLUSIONS: ERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa....

  15. Differences in treatment patterns among patients with castration-resistant prostate cancer treated by oncologists versus urologists in a US managed care population

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    Engel-Nitz NM

    2011-07-01

    Full Text Available Nicole M Engel-Nitz1, Berhanu Alemayehu2, David Parry3, Faith Nathan21Innovus, Eden Prairie, MN, USA; 2AstraZeneca, Wilmington, DE, USA; 3AstraZeneca UK, London, UKObjective: Differences in treatment patterns, health care resource utilization, and costs between patients with castration-resistant prostate cancer (CRPC treated by oncologists and those treated by urologists were examined.Methods: Patients aged ≥40 with CRPC were identified using claims from a large US managed health care plan between July 2001 and December 2007. A 6-month baseline period was used to assess patient characteristics. Patients with visits to an urologist, without visits to an oncologist, were assigned to the urology cohort, and patients with visits to an oncologist, with or without visits to an urologist, were assigned to the oncology cohort. Treatment patterns, health care resource utilization, and costs during a variable follow-up period were compared between cohorts using descriptive statistics and Lin's regression.Results: The urology cohort had fewer comorbid illnesses (P < 0.001 and patients were less likely to have other cancers during baseline (P < 0.001 or to die during follow-up (P = 0.004 compared with the oncology cohort. The oncology cohort patients were significantly more likely to have a claim for hormones (74.5% vs 61.1%; P < 0.001, chemotherapy (46.9% vs 10.2%, P < 0.001, and radiation (22.3% vs 3.7%, P < 0.0001 over follow-up. Mean unadjusted health care costs were higher in the oncology vs the urology cohort (US$31,896 vs US$15,318, respectively; P < 0.001. At 6 years follow-up, cumulative adjusted CRPC-specific costs were significantly higher among patients treated by oncologists with chemotherapy than among patients treated by urologists.Conclusion: CRPC patients treated by oncologists had greater use of hormones, chemotherapy, and radiation; higher percentages of patients with inpatient stays, emergency room, and ambulatory visits; and higher

  16. Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells.

    Science.gov (United States)

    Johnston, Paul A; Nguyen, Minh M; Dar, Javid A; Ai, Junkui; Wang, Yujuan; Masoodi, Khalid Z; Shun, Tongying; Shinde, Sunita; Camarco, Daniel P; Hua, Yun; Huryn, Donna M; Wilson, Gabriela Mustata; Lazo, John S; Nelson, Joel B; Wipf, Peter; Wang, Zhou

    2016-05-01

    Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second-generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide. PMID:27187604

  17. ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L.

    Science.gov (United States)

    Wang, Ronghao; Lin, Wanying; Lin, Changyi; Li, Lei; Sun, Yin; Chang, Chawnshang

    2016-08-28

    Androgen deprivation therapy (ADT) with the newly developed powerful anti-androgen enzalutamide (Enz, also known as MDV3100) has promising therapeutic effects to suppress castration resistant prostate cancer (CRPC) and extending patients' lives an extra 4.8 months. However, most Enz therapy eventually fails with the development of Enz resistance. The detailed mechanisms how CRPC develops Enz resistance remain unclear and may involve multiple mechanisms. Among them, the induction of the androgen receptor (AR) mutant AR-F876L in some CRPC patients may represent one driving force that confers Enz resistance. Here, we demonstrate that the AR degradation enhancer, ASC-J9(®), not only degrades wild-type AR, but also has the ability to target AR-F876L. The consequence of suppressing AR-F876L may then abrogate AR-F876L mediated CRPC cell proliferation and metastasis. Thus, developing ASC-J9(®) as a new therapeutic approach may represent a novel therapy to better suppress CRPC that has already developed Enz resistance. PMID:27233475

  18. Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35.

    Science.gov (United States)

    Jung, Mi-Jeong; Moon, Young-Chan; Cho, Ik-Hyun; Yeh, Jung-Yong; Kim, Sun-Eui; Chang, Wha-Seok; Park, Seung-Young; Song, Chang-Seon; Kim, Hwi-Yool; Park, Keun-Kyu; McOrist, Steven; Choi, In-Soo; Lee, Joong-Bok

    2005-03-01

    Immunocastration is a considerable alternative to a surgical castration method especially in male animal species for alleviating unwanted male behaviors and characteristics. Induction of high titer of antibody specific for gonadotropin-releasing hormone (GnRH) correlates with the regression of testes. Fusion proteins composed of canine GnRH and T helper (Th) cell epitope p35 originated from canine distemper virus (CDV) F protein and goat rotavirus VP6 protein were produced in E. coli. When these fusion proteins were injected to male dogs which were previously immunized with CDV vaccine, the fusion protein of GnRH-CDV Th cell epitope p35 induced much higher antibody than that of GnRH-rotavirus VP6 protein or GnRH alone. The degeneration of spermatogenesis was also verified in the male dogs immunized with the fusion protein of GnRH-CDV Th cell epitope p35. These results indicate that canine GnRH conjugated to CDV Th cell epitope p35 acted as a strong immunogen and the antibody to GnRH specifically neutralized GnRH in the testes. This study also implies a potential application of GnRH-based vaccines for immunocastration of male pets. PMID:15785119

  19. ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L.

    Science.gov (United States)

    Wang, Ronghao; Lin, Wanying; Lin, Changyi; Li, Lei; Sun, Yin; Chang, Chawnshang

    2016-08-28

    Androgen deprivation therapy (ADT) with the newly developed powerful anti-androgen enzalutamide (Enz, also known as MDV3100) has promising therapeutic effects to suppress castration resistant prostate cancer (CRPC) and extending patients' lives an extra 4.8 months. However, most Enz therapy eventually fails with the development of Enz resistance. The detailed mechanisms how CRPC develops Enz resistance remain unclear and may involve multiple mechanisms. Among them, the induction of the androgen receptor (AR) mutant AR-F876L in some CRPC patients may represent one driving force that confers Enz resistance. Here, we demonstrate that the AR degradation enhancer, ASC-J9(®), not only degrades wild-type AR, but also has the ability to target AR-F876L. The consequence of suppressing AR-F876L may then abrogate AR-F876L mediated CRPC cell proliferation and metastasis. Thus, developing ASC-J9(®) as a new therapeutic approach may represent a novel therapy to better suppress CRPC that has already developed Enz resistance.

  20. A Joint Model for the Kinetics of CTC Count and PSA Concentration During Treatment in Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Wilbaux, M; Tod, M; De Bono, J; Lorente, D; Mateo, J; Freyer, G; You, B; Hénin, E

    2015-05-01

    Assessment of treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) is limited by frequent nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is a promising surrogate marker that may replace the widely used prostate-specific antigen (PSA). The purpose of this study was to quantify the dynamic relationships between the longitudinal kinetics of these markers during treatment in patients with mCRPC. Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling. Linked with survival, this model would potentially be useful for predicting treatment efficacy during drug development or for therapeutic adjustment in treated patients. PMID:26225253

  1. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

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    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  2. Efeito da trimegestona sobre o tecido mamário de ratas castradas Effect of trimegestone on mammary gland of castrated rats

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    Luciana de Oliveira Marques

    2011-07-01

    Full Text Available OBJETIVO: Avaliar o efeito da trimegestona sobre a proliferação celular do tecido mamário de ratas castradas. MÉTODOS: Foram utilizadas 45 ratas adultas e virgens, da linhagem Wistar, submetidas à castração. Após o 60º dia da castração, confirmado o hipoestrogenismo, os animais foram divididos aleatoriamente em três grupos, conforme o tratamento proposto: controle (n=15 recebeu soro fisiológico 0,9%; estrogênio (n=15 recebeu 17 beta-estradiol; e combinado (n=15 recebeu 17 beta-estradiol associado à trimegestona, todos por 60 dias consecutivos. Após o término do tratamento, procedeu-se a exérese das mamas inguinais, destinadas a análise morfométrica pela coloração de hematoxilina e eosina (HE e imuno-histoquímica pela quantificação do anticorpo anti-PCNA no tecido mamário, seguido de eutanásia. Os parâmetros morfométricos avaliados foram: proliferação celular epitelial, atividade secretora e alteração do estroma mamário. Ocorreram nove óbitos durante o experimento. As variáveis foram submetidas à análise estatística adotando-se como significante pPURPOSE: To evaluate the efect of trimegestone on the histological changes of the mammary tissue of castrated rats. METHODS: Forty-five virgin female Wistar rats were used after oophorectomy. Sixty days after surgery, with hypoestrogenisms confirmed, the experimental rats were randomly assigned to three groups of 15 animals each, when then the specific treatment for each group was started. The control group (C and experimental groups 1 and 2 respectively received 0.9% saline solution, 17-beta-estradiol and 17-beta-estradiol in combination with trimegestone for 60 consecutive days. After the end of treatment , the inguinal mammary glands were removed, stained with hematoxylin and eosin (HE for morphometry and examined by immunohistochemistry for the quantification of anti-PCNA antibody in the mammary tissue, followed by euthanasia. The morphometric parameters

  3. Phase I Dose-Escalation Study of the Novel Anti-androgen BMS-641988 in Patients with Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Rathkopf, Dana; Liu, Glenn; Carducci, Michael A; Eisenberger, Mario A; Anand, Aseem; Morris, Michael J; Slovin, Susan F; Sasaki, Yasutsuna; Takahashi, Shunji; Ozono, Seiichiro; Fung, Nga Kit Eliza; Cheng, Shinta; Gan, Jinping; Gottardis, Marco; Obermeier, Mary T.; Reddy, Jyotsna; Zhang, Steven; Vakkalagadda, Blisse J.; Wilding, George; Scher, Howard I.

    2011-01-01

    Purpose BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both in vitro and in vivo prostate cancer models. A first-in-man phase I study was conducted to define the safety and tolerability of oral BMS-641988 in patients with castration-resistant prostate cancer (CRPC). Experimental Design Doses were escalated from 5 to 150 mg based on discrete pharmacokinetic parameters in cohorts of 3 to 6 subjects. After establishing safety with 20 mg of BMS-641988 in the United States, a companion study was opened in Japan to assess differences in drug metabolism between populations. Results Sixty-one men with CRPC were treated with daily BMS-641988. The pharmacokinetics of BMS-641988 and its active metabolites were proportional to dose. One patient experienced an epileptic seizure at a dose of 60 mg administered twice. Despite achieving target drug exposures, anti-tumor activity was limited to 1 partial response. Seventeen of 23 evaluable patients (74%) exhibited stable disease on imaging (median 15 weeks; range 8–32), and 10 of 61 patients (16%) achieved a ≥30%. decline in levels of prostate-specific antigen (PSA). Partial agonism was seen within the context of this study upon removal of the drug as evidenced by a decrease in PSA. Conclusions Although the clinical outcomes of predominantly stable disease and partial agonism were similar to what was observed in the preclinical evaluation of the compound, the limited anti-tumor activity of BMS-641988 at therapeutic dose levels coupled with an episode of seizure activity led to study closure. PMID:21131556

  4. Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Binder, Moritz; Zhang, Ben Y; Hillman, David W; Kohli, Rhea; Kohli, Tanvi; Lee, Adam; Kohli, Manish

    2016-01-01

    Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54-90); the median prostate-specific antigen was 66 ng/dL (0.1-99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07-0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39-3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID:27409606

  5. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT.

    Science.gov (United States)

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-08-01

    In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70-155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated.At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD.PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  6. RADIATION SAFETY CONSIDERATIONS FOR THE USE OF 223RaCl2 DE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER

    Science.gov (United States)

    Dauer, Lawrence T.; Williamson, Matthew J.; Humm, John; O’Donoghue, Joseph; Ghani, Rashid; Awadallah, Robert; Carrasquillo, Jorge; Pandit-Taskar, Neeta; Aksnes, Anne-Kirsti; Biggin, Colin; Reinton, Vigdis; Morris, Michael; St Germain, Jean

    2016-01-01

    The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (223RaCl2), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg−1 body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered 223Ra dichloride were typically less than 2 μSv h−1 MBq−1 on contact and averaged 0.02 μSv h−1 MBq−1 at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5–11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that 223Ra may provide a new standard of care for patients with CRPC and bone metastases. PMID:24562070

  7. Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline

    Science.gov (United States)

    Basch, Ethan; Loblaw, D. Andrew; Oliver, Thomas K.; Carducci, Michael; Chen, Ronald C.; Frame, James N.; Garrels, Kristina; Hotte, Sebastien; Kattan, Michael W.; Raghavan, Derek; Saad, Fred; Taplin, Mary-Ellen; Walker-Dilks, Cindy; Williams, James; Winquist, Eric; Bennett, Charles L.; Wootton, Ted; Rumble, R. Bryan; Dusetzina, Stacie B.; Virgo, Katherine S.

    2014-01-01

    Purpose To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). Methods The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. Results When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 (223Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. Recommendations Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or 223Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to

  8. A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer.

    Directory of Open Access Journals (Sweden)

    Tie Zhou

    Full Text Available To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC.A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily. Primary end point was overall survival, and secondary end points were events progression-free survival (PFS, response rate, response duration. Quality of life (QoL was also assessed in both treatment groups.The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46-0.86. Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155. Pain response rate was higher in D3P arm (61.11%, P = 0.0011 than in M3P (23.08% arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm.Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain.clinicaltrials.gov NCT00436839.

  9. Effects of androgen deprivation therapy and bisphosphonate treatment on bone in patients with metastatic castration-resistant prostate cancer: results from the University of Washington Rapid Autopsy Series.

    Science.gov (United States)

    Morrissey, Colm; Roudier, Martine P; Dowell, Alex; True, Lawrence D; Ketchanji, Melanie; Welty, Christopher; Corey, Eva; Lange, Paul H; Higano, Celestia S; Vessella, Robert L

    2013-02-01

    Qualitative and quantitative bone features were determined in nondecalcified and decalcified bone from 20 predetermined bone sites in each of 44 patients who died with castration-resistant prostate cancer (CRPC), some of which received bisphosphonate treatment (BP) in addition to androgen-deprivation therapy (ADT). Thirty-nine of the 44 patients (89%) had evidence of bone metastases. By histomorphometric analysis, these bone metastases were associated with a range of bone responses from osteoblastic to osteolytic with a wide spectrum of bone responses often seen within an individual patient. Overall, the average bone volume/tissue volume (BV/TV) was 25.7%, confirming the characteristic association of an osteoblastic response to prostate cancer bone metastasis when compared with the normal age-matched weighted mean BV/TV of 14.7%. The observed new bone formation was essentially woven bone, and this was a localized event. In comparing BV/TV at metastatic sites between patients who had received BP treatment and those who had not, there was a significant difference (28.6% versus 19.3%, respectively). At bone sites that were not invaded by tumor, the average BV/TV was 10.1%, indicating significant bone loss owing to ADT that was not improved (11%) in those patients who had received BPs. Surprisingly, there was no significant difference in the number of osteoclasts present at the metastatic sites between patients treated or not treated with BPs, but in bone sites where the patient had been treated with BPs, giant osteoclasts were observed. Overall, 873 paraffin-embedded specimens and 661 methylmethacrylate-embedded specimens were analyzed. Our results indicate that in CRPC patients, ADT induces serious bone loss even in patients treated with BP. Furthermore, in this cohort of patients, BP treatment increased BV and did not decrease the number of osteoclasts in prostate cancer bone metastases compared with bone metastases from patients who did not receive BP.

  10. Treatment evolution for metastatic castration-resistant prostate cancer with recent introduction of novel agents: retrospective analysis of real-world data.

    Science.gov (United States)

    Flaig, Thomas W; Potluri, Ravi C; Ng, Yvette; Todd, Mary B; Mehra, Maneesha

    2016-02-01

    Despite increasing drug treatment options for metastatic castration-resistant prostate cancer (mCRPC) patients, real-world treatment data are lacking. We conducted retrospective analyses of commercial claims and electronic medical record (EMR) databases to understand how treatment patterns for mCRPC have changed in a US-based real-world population. Truven Health Analytics MarketScan(®) (2000-2013) and EMR (2004-2013) databases were used to identify patients with an index prostate cancer diagnosis (ICD-9 codes 185X or 233.4X) and prescription claims for an mCRPC drug (mitoxantrone, estramustine, docetaxel, sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, or radium-223). Regimen analyses for first line of therapy (LOT1), second line of therapy, and beyond were performed among cohorts based on year of first mCRPC drug usage. mCRPC drug usage and treatment duration were compared across cohorts and age groups within each cohort. The commercial claims cohort yielded 3437 evaluable patients. Most men (91%) commencing mCRPC treatment had docetaxel as LOT1 in 2010; this number had declined to 15% in 2013. In 2013, 67% and 9% of patients used abiraterone acetate and enzalutamide, respectively, as LOT1. Among both commercial claims and EMR cohorts, treatment pattern changes were most pronounced in men aged >80 years, and median treatment duration for some mCRPC drugs was shorter than expected based on available clinical trial information. These results demonstrate a shift in mCRPC treatments during the past 5 years, with greater use of newer noncytotoxic treatments than docetaxel. These real-world data aid in understanding the changing role of chemotherapy in the management of mCRPC.

  11. Differences in treatment patterns among patients with castration-resistant prostate cancer treated by oncologists versus urologists in a US managed care population

    International Nuclear Information System (INIS)

    Differences in treatment patterns, health care resource utilization, and costs between patients with castration-resistant prostate cancer (CRPC) treated by oncologists and those treated by urologists were examined. Patients aged ≥40 with CRPC were identified using claims from a large US managed health care plan between July 2001 and December 2007. A 6-month baseline period was used to assess patient characteristics. Patients with visits to an urologist, without visits to an oncologist, were assigned to the urology cohort, and patients with visits to an oncologist, with or without visits to an urologist, were assigned to the oncology cohort. Treatment patterns, health care resource utilization, and costs during a variable follow-up period were compared between cohorts using descriptive statistics and Lin’s regression. The urology cohort had fewer comorbid illnesses (P < 0.001) and patients were less likely to have other cancers during baseline (P < 0.001) or to die during follow-up (P = 0.004) compared with the oncology cohort. The oncology cohort patients were significantly more likely to have a claim for hormones (74.5% vs 61.1%; P < 0.001), chemotherapy (46.9% vs 10.2%, P < 0.001), and radiation (22.3% vs 3.7%, P < 0.0001) over follow-up. Mean unadjusted health care costs were higher in the oncology vs the urology cohort (US$31,896 vs US$15,318, respectively; P < 0.001). At 6 years follow-up, cumulative adjusted CRPC-specific costs were significantly higher among patients treated by oncologists with chemotherapy than among patients treated by urologists. CRPC patients treated by oncologists had greater use of hormones, chemotherapy, and radiation; higher percentages of patients with inpatient stays, emergency room, and ambulatory visits; and higher health care costs, than patients treated by urologists

  12. Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary.

    Science.gov (United States)

    Ning, Yangmin M; Pierce, William; Maher, V Ellen; Karuri, Stella; Tang, Sheng-Hui; Chiu, Haw-Jyh; Palmby, Todd; Zirkelbach, Jeanne Fourie; Marathe, Dhananjay; Mehrotra, Nitin; Liu, Qi; Ghosh, Debasis; Cottrell, Christy L; Leighton, John; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

    2013-11-15

    This article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53-0.75; P < 0.0001]. The median overall survival durations were 18.4 months and 13.6 months in the enzalutamide and placebo arms, respectively. The most common adverse reactions (≥10%) included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures occurred in 0.9% of patients on enzalutamide compared with no patients on the placebo arm. Overall, the FDA's review and analyses of the submitted data confirmed that enzalutamide had a favorable benefit-risk profile in the study patient population, thus supporting its use for the approved indication. The recommended dose is 160 mg of enzalutamide administered orally once daily. Enzalutamide represents the third product that the FDA has approved in the same disease setting within a period of 2 years. Clin Cancer Res; 19(22); 6067-73. ©2013 AACR.

  13. Impact of pre-treatment prostate tissue androgen content on the prediction of castration-resistant prostate cancer development in patients treated with primary androgen deprivation therapy.

    Science.gov (United States)

    Shibata, Y; Suzuki, K; Arai, S; Miyoshi, Y; Umemoto, S; Masumori, N; Kamiya, N; Ichikawa, T; Kitagawa, Y; Mizokami, A; Sugimura, Y; Nonomura, N; Sakai, H; Honma, S; Kubota, Y

    2013-05-01

    Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients' prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0 ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation. PMID:23444052

  14. Novel flutamide regulated genes in the rat ventral prostate: differential modulation of their expression by castration and flutamide treatments%大鼠腹侧前列腺中受氟他胺调控的新基因:去势和氟他胺处理对其表达的调控

    Institute of Scientific and Technical Information of China (English)

    A. M. Limaye; I. Asangani; N. Bora; P. Kondaiah

    2007-01-01

    Aim: To identify flutamide regulated genes in the rat ventral prostate. Methods: Total RNA from ventral prostates of control and flutamide treated rats were isolated. Differentially expressed transcripts were identified using differential display reverse transcriptase polymerase chain reaction. The effect of castration on the expression of flutamideregulated transcripts was studied. Results: We have identified β2-microglobulin, cytoplasmic FMR1 interacting protein 2 and pumilio 1 as flutamide induced and spermine binding protein and ribophorin Ⅱ as flutamide repressed targets in the rat ventral prostate. Although flutamide treatment caused an induction of pumilio 1 mRNA, castration had no effect. Conclusion: Castration and flutamide treatments exert differential effects on gene expression. Flutamide might also have direct AR independent effects, which might have implications in the emergence of androgen independent prostate cancer and the failure of flutamide therapy.

  15. O trauma sexual e a angústia de castração: percurso freudiano à luz das contribuições de Lacan Sexual trauma and castration anguish: freudian courses in light of Lacan's contributions

    Directory of Open Access Journals (Sweden)

    Luiza Vieira Couto

    2009-01-01

    Full Text Available Este trabalho tem como objetivo articular os conceitos de trauma sexual e angústia de castração a partir dos textos freudianos e à luz das contribuições de Lacan. Em Freud, estes conceitos acompanham a construção da psicanálise enquanto campo de investigação do inconsciente. O inconsciente nos indica o vazio fundamental que movimenta o desejo, a ausência do objeto. A fantasia, através do que se orienta o desejo, representa a permanência do objeto faltoso, a alienação do eu no Ideal de um gozo fálico. A angústia de castração funciona como sinal para a atuação dos mecanismos de defesa do eu, cujo último véu é a reivindicação fálica. Esta, articulada à angústia de castração, surge como "limite intransponível" da psicanálise. A proposta de Lacan é ir para além da angústia de castração, retornando, ao seu modo, ao conceito de trauma sexual.The objective of the present study is to articulate the definition of sexual trauma and castration anguish according to Freudian texts and Lacan's contributions. For Freud, these definitions follow psychoanalysis as a field that investigates the unconscious. The unconscious indicates the fundamental emptiness that moves the desire, the absence of the object. Fantasy, as a desire guide, represents the permanence of the missing object, the alienation of the ego within the ideal of the phallic pleasure. Castration anguish works as a sign for ego defense mechanisms to come into play, in which the last instance is the phallic pleasure. This, articulated to castration anguish, comes as a "non trespassing border" of psychoanalysis. Lacan's proposal is to go beyond castration anguish, returning, on his way, to the definition of the sexual trauma.

  16. Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Kohli M

    2015-07-01

    Full Text Available Manish Kohli,1 Charles YF Young,2 Donald J Tindall,2 Debashis Nandy,1 Kyle M McKenzie,3 Graham H Bevan,4 Krishna Vanaja Donkena5 1Department of Oncology, 2Department of Urology, 3Department of Geriatric Medicine, Mayo Clinic, Rochester, MN, 4University of Rochester Medical Center, Rochester, NY, 5Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA Abstract: This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration-resistant prostate cancer (CRPC. RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing before and after docetaxel treatment using the Illumina’s HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two-fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5. In addition, post-docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8. Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3

  17. {sup 18}F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

    Energy Technology Data Exchange (ETDEWEB)

    De Giorgi, Ugo; Conteduca, Vincenza; Burgio, Salvatore Luca; Menna, Cecilia; Rossi, Lorena; Amadori, Dino [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy); Caroli, Paola; Paganelli, Giovanni; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Diagnostic Nuclear Medicine Unit, Meldola (Italy); Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [Morgagni-Pierantoni Hospital, Nuclear Medicine Unit, Forli (Italy)

    2015-07-15

    We investigated the role of {sup 18}F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response

  18. Androgen suppresses the proliferation of androgen receptor-positive castration-resistant prostate cancer cells via inhibition of Cdk2, CyclinA, and Skp2.

    Directory of Open Access Journals (Sweden)

    John M Kokontis

    Full Text Available The majority of prostate cancer (PCa patient receiving androgen ablation therapy eventually develop castration-resistant prostate cancer (CRPC. We previously reported that androgen treatment suppresses Skp2 and c-Myc through androgen receptor (AR and induced G1 cell cycle arrest in androgen-independent LNCaP 104-R2 cells, a late stage CRPC cell line model. However, the mechanism of androgenic regulation of Skp2 in CRPC cells was not fully understood. In this study, we investigated the androgenic regulation of Skp2 in two AR-positive CRPC cell line models, the LNCaP 104-R1 and PC-3AR Cells. The former one is an early stage androgen-independent LNCaP cells, while the later one is PC-3 cells re-expressing either wild type AR or mutant LNCaP AR. Proliferation of LNCaP 104-R1 and PC-3AR cells is not dependent on but is suppressed by androgen. We observed in this study that androgen treatment reduced protein expression of Cdk2, Cdk7, Cyclin A, cyclin H, Skp2, c-Myc, and E2F-1; lessened phosphorylation of Thr14, Tyr15, and Thr160 on Cdk2; decreased activity of Cdk2; induced protein level of p27(Kip1; and caused G1 cell cycle arrest in LNCaP 104-R1 cells and PC-3AR cells. Overexpression of Skp2 protein in LNCaP 104-R1 or PC-3AR cells partially blocked accumulation of p27(Kip1 and increased Cdk2 activity under androgen treatment, which partially blocked the androgenic suppressive effects on proliferation and cell cycle. Analyzing on-line gene array data of 214 normal and PCa samples indicated that gene expression of Skp2, Cdk2, and cyclin A positively correlates to each other, while Cdk7 negatively correlates to these genes. These observations suggested that androgen suppresses the proliferation of CRPC cells partially through inhibition of Cyclin A, Cdk2, and Skp2.

  19. Androgen suppresses the proliferation of androgen receptor-positive castration-resistant prostate cancer cells via inhibition of Cdk2, CyclinA, and Skp2.

    Science.gov (United States)

    Kokontis, John M; Lin, Hui-Ping; Jiang, Shih Sheng; Lin, Ching-Yu; Fukuchi, Junichi; Hiipakka, Richard A; Chung, Chi-Jung; Chan, Tzu-Min; Liao, Shutsung; Chang, Chung-Ho; Chuu, Chih-Pin

    2014-01-01

    The majority of prostate cancer (PCa) patient receiving androgen ablation therapy eventually develop castration-resistant prostate cancer (CRPC). We previously reported that androgen treatment suppresses Skp2 and c-Myc through androgen receptor (AR) and induced G1 cell cycle arrest in androgen-independent LNCaP 104-R2 cells, a late stage CRPC cell line model. However, the mechanism of androgenic regulation of Skp2 in CRPC cells was not fully understood. In this study, we investigated the androgenic regulation of Skp2 in two AR-positive CRPC cell line models, the LNCaP 104-R1 and PC-3AR Cells. The former one is an early stage androgen-independent LNCaP cells, while the later one is PC-3 cells re-expressing either wild type AR or mutant LNCaP AR. Proliferation of LNCaP 104-R1 and PC-3AR cells is not dependent on but is suppressed by androgen. We observed in this study that androgen treatment reduced protein expression of Cdk2, Cdk7, Cyclin A, cyclin H, Skp2, c-Myc, and E2F-1; lessened phosphorylation of Thr14, Tyr15, and Thr160 on Cdk2; decreased activity of Cdk2; induced protein level of p27(Kip1); and caused G1 cell cycle arrest in LNCaP 104-R1 cells and PC-3AR cells. Overexpression of Skp2 protein in LNCaP 104-R1 or PC-3AR cells partially blocked accumulation of p27(Kip1) and increased Cdk2 activity under androgen treatment, which partially blocked the androgenic suppressive effects on proliferation and cell cycle. Analyzing on-line gene array data of 214 normal and PCa samples indicated that gene expression of Skp2, Cdk2, and cyclin A positively correlates to each other, while Cdk7 negatively correlates to these genes. These observations suggested that androgen suppresses the proliferation of CRPC cells partially through inhibition of Cyclin A, Cdk2, and Skp2.

  20. Volume of Bone Metastasis Assessed with Whole-Body Diffusion-weighted Imaging Is Associated with Overall Survival in Metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Perez-Lopez, Raquel; Lorente, David; Blackledge, Matthew D; Collins, David J; Mateo, Joaquin; Bianchini, Diletta; Omlin, Aurelius; Zivi, Andrea; Leach, Martin O; de Bono, Johann S; Koh, Dow-Mu; Tunariu, Nina

    2016-07-01

    Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26807894

  1. [Chemical castration in homosexual pedophilia].

    Science.gov (United States)

    Czeizel, E

    1996-01-01

    The treatment of reducing sexual drive with antiandrogenic cyproterone acetate in a man with homosexual paedophilia is shown with the summary of rules for the use of cyproterone acetate in the therapy of sexual deviations.

  2. Efeitos da Corticosteroidoterapia na Uretra e na Bexiga de Ratas Castradas antes e durante Reposição Estrogênica Effects of Corticosteroids in the Urethra and Bladder of Castrated Female Rats before and during Estrogen Replacement Teraphy

    Directory of Open Access Journals (Sweden)

    João Batista dos Santos Junior

    2000-12-01

    five groups. Group I - ten castrated female rats; Group II - eleven castrated female rats which receivedintraperitoneally 15 mg/kg weight prednisolone, for 26 days; Group III - twelve castrated female rats which received the same amount of corticosteroid, during the same time, and subcutaneously 10 mg/kg 17 beta-estradiol, in the last five days before they were sacrificed; Group IV - eleven castrated rats which received placebo for 26 days; and Group V - no castrated female rats which received the same dose of corticosteroid during the same time as in Group II. Results: we observed an average of 1.8 vessels in the bladder of the castrated group which received corticosteroid, a similar number to that of those which received corticosteroid and estrogen, compared with 0.8 vessel in the placebo group. Regarding the urethra, 0.7 vessel was observed in the group which received corticosteroid, as compared with 0.9 vessel in the group treated with corticosteroid associated with estrogen and 0.4 in the placebo group. Regarding the mucous membrane, the vesical epithelium thickness of 14.1 mm in the placebo group increased to 20.6 mm in that with corticosteroid and to 22.6 mm in that with corticosteroid plus estrogen. The urethral epithelium thickness of 12.4 mm in the placebo group increased to 15.1 mm in the group with corticosteroid and to 16.7 mm in that with corticosteroid plus estrogen. Conclusion: corticosteroids significantly increased the vascularization and the thickness of the vesical and urethral epithelia of castrated female rats.

  3. Efeito da castração pré-púbere sobre o desenvolvimento corporal de equinos - DOI: 10.4025/actascianimsci.v26i2.1883 Pre-puberty castration effect on equine body development - DOI: 10.4025/actascianimsci.v26i2.1883

    Directory of Open Access Journals (Sweden)

    Nilva Aparecida Nicolao Fonseca

    2004-04-01

    Full Text Available Foi realizado um experimento com o objetivo de avaliar o efeito da castração pré-púbere sobre o desenvolvimento corporal de cavalos de trabalho. Foram utilizados 18 potros meio-irmãos paternos, meio sangue mangalarga, dos quais 8 foram castrados aos 2 meses de idade. As características avaliadas foram as alturas da cernelha, do dorso, da anca, do costado e do esterno, os comprimentos do corpo e da garupa, as larguras do costado, da bacia, da anca e do peito e os perímetros da canela e torácico, as quais foram medidas aos 2, 12 e 24 meses de idade. Foram avaliados, também aos 24 meses, os índices de carga, de compacidade, corporal, anamorfósico, de altura peitoral e dactilo-torácico. Observou-se que, aos 24 meses, não ocorreram diferenças significativas entre os animais castrados e os não-castrados, exceto para peso vivo, perímetro torácico e índice de compacidade, que foram superiores para os animais não-castrados. Conclui-se que é viável a castração de animais jovens.Aiming to evaluate the effect of pre-puberty castration on traction horses' body development, the experiment was carried out with 18 cross breeding Mangalarga foals. The animals belonged to the same stallion offspring and were castrated at 2 months old. The following characteristics were measured at ages 2, 12 and 24 months: the hights of withers, back chine, hook, ribs and chest floor, the lengths of body and rump, the widths of thurl, hook and chest and the perimeters of limbs and thorax. Besides, loading, capacity, body, morphological, chest and dactyl-thorax indexes were also measured. The results showed that there were not significant differences between castrated and non-castrated animals for almost all measured characteristics. However, castrated horses had greater liveweight, thorax perimeter and index capacity than non-castrated animals. Thus, it was concluded that pre-puberty castration is feasible.

  4. 转移性去势抵抗性前列腺癌化疗后预后的影响因素%Factors Influencing Prognosis of Metastatic Castration-resistant Prostate Cancer after Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    庞华

    2014-01-01

    Objective To investigate prognostic factors of metastatic castration-resistant prostate cancer ( mCRPC ) trea-ted with docetaxel chemotherapy .Methods Age,Gleason score ,prostate-specific antigen ,blood baseline condition and hormone-sensitive time of 46 patients with mCRPC were recorded .Results Overall survival time of all patients was 3-45 months,the aver-age survival time was (21.34 ±2.13) months,median survival time was 19.36 months;cox regression analysis showed that Glea-son score,hemoglobin,hormone-sensitive time were related with the patient's survival time,RR values were 1.782,2.363 and 2.012,and P<0.05.Conclusion Gleason score,hemoglobin concentration ,and hormone-sensitive time before chemotherapy are prognostic factors of metastatic castration resistant prostate cancer .%目的:探讨采用多西紫杉醇化疗的转移性去势抵抗性前列腺癌( metastatic castration-resistant prostate canc-er,MCRPC)患者预后影响因素。方法以转移性去势抵抗性前列腺癌患者46例作为观察对象,记录患者化疗前年龄、Gleason评分、前列腺特异抗原(prostate-specific antigen,PSA)值、血常规等基线情况及激素敏感时间。结果患者总生存时间为3~45个月,平均生存期为(21.34±2.13)个月,中位生存时间为19.36个月;Cox回归结果提示,Gleason评分、血红蛋白水平、激素敏感时间与患者生存时间相关,RR值分别为1.782、2.363和2.012,且P<0.05。结论多西他赛化疗前Gleason评分、血红蛋白浓度及激素敏感时间,是转移性去势抵抗性前列腺癌患者的预后因素。

  5. Infestation pattern and parasitic castration of the crustacean Riggia paranensis (Crustacea: Cymothoidea on the fresh water fish Cyphocharax gilbert (Teleostei: Curimatidae

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    Juliana de Souza Azevedo

    2006-09-01

    Full Text Available Cyphocharax gilbert infested by Riggia paranensis shows parasitic castration. The prevalence of parasitism in C. gilbert varied among different environments, being higher in the middle rio Itabapoana. Fish were collected monthly using two cast nets (thrown 30 times during the day and gillnets kept in the river during 12 hour, from sunset to sunrise, between September 1997 and August 2000. Infestation pattern was investigated on 1358 specimens. Most of them were infested (57.9%, with one or two parasites; the majority (62.9% was collected during the rainy season (spring-summer. The parasite did not show preference for sex or size of hosts. A total of 91.5% of the 511 examined parasites had a body size that represented 10.1% to 20% of host standard length. The reproductive condition of 311 specimens of R. paranensis was analyzed checking the presence of oocytes in the ovarian and eggs or embryos in the marsupium. Nearly 73% of them were at reproductive phase, and had a body size that represented 5.1% to 20% of host standard length. The size of the immature parasites varied from 0.1% to 5% of the host size. The results suggest that R. paranensis may adopt a fast growth rate strategy and increase the investment in reproduction when they occupy most of the host's pericardial space.Cyphocharax gilbert infestado por Riggia paranensis apresenta castração parasitária. A prevalência do parasito varia entre diferentes ambientes, sendo maior no trecho médio do rio Itabapoana. Os peixes foram coletados mensalmente neste rio usando duas tarrafas (lançadas por 30 vezes durante o dia e redes de espera por 12 horas, do crepúsculo ao amanhecer, entre setembro de 1997 e agosto de 2000. O padrão de infestação foi investigado em 1358 peixes. Peixes infestados apresentaram um ou dois parasitos, representando 57,9% da população e a maioria deles (62,9% foi coletada no período de maior precipitação (primavera-verão. O parasito não apresentou prefer

  6. Alveolar Bone Reduction Curves of Castrated Rats after Incisors Extraction%去势大鼠下切牙拔除后牙槽骨吸收曲线的绘制

    Institute of Scientific and Technical Information of China (English)

    兰泽栋; 郑雅心; 吴琳琳

    2013-01-01

    目的:研究去势大鼠下切牙拔除后牙槽骨吸收曲线.方法:6组雄性Wistar大鼠在全麻下去势并拔除右下切牙,分别于0、1、2、4、8、12周处死.用软X线拍摄大鼠下颌骨,测量并计算出颊侧、舌侧牙槽骨高度和宽度的吸收值绘制曲线.结果:0~12周颊、舌侧牙槽骨高度吸收值表现为先快速增加后快速下降的曲线;而宽度吸收值未见明显变化.结论:该曲线可作为预防牙槽骨吸收的基础性研究.%Objective:To investigate the alveolar bones reduction curves of of castrated rats after incisors extraction.Methods:Six groups of Wistar rats were castrated after general anesthesia and the right lower incisors were extracted respectively.All rats were sacrificed at 0,1,2,4,8,12 weeks after tooth-extractions.After photographing the rats' mandibules with molybdenum target soft X-ray,we measured and calculated the vertical and horizontal dimension changes of buccal and lingual sides to draw curves.Results:The vertical resorption of buccal and lingual sides of alveolar bones appear to be rapid loss at first few weeks and declined dramatically thereafter during the 12 weeks.However,there were no significant changes of horizontal dimension.Conclusion:These curves can be a theoretical basis for preventing residual alveolar ridge resorption.

  7. 手术去势对晚期前列腺癌患者生活质量的影响%The quality of life in man after treatment of advanced prostate cancer by surgical castration

    Institute of Scientific and Technical Information of China (English)

    陈伟; 余志贤; 谢辉; 张方毅; 王思齐; 邓哲宪; 吴秀玲; 翁志梁

    2008-01-01

    目的 调查手术去势对晚期前列腺癌患者生活质量的影响.方法 采用EORTCQLQ-C30总量表和QLQ-PR25子量表调查69例接受手术去势的晚期前列腺癌患者患病前、治疗后6个月和治疗后12个月3个时闯点的生活质量情况.结果 手术去势虽然能缓解全身或局部疼痛(P<0.01),并改善排尿症状(P<0.01),且患者感觉总体健康状况有好转(P<0.01),但术后患者躯体(P<0.05)、角色(P<0.01)、情绪(P<0.01)、认知(P<0.05)、社会(P<0.05或<0.01)等功能均有不同程度下降,且失眠增多(P<0.05)、疲倦加剧(P<0.01),治疗相关症状如潮红与乳房胀痛等显著出现(P<0.01),性趣明显下降甚至丧失(P<0.01),特别是彻底丧失了正常的性生活.结论 手术去势对前列腺癌患者的机体与心理均有不同程度的影响,尤其是性功能方面有不可逆性损害.%Objective To investigate the quality of life in man after treatment of advanced prostate cancer by surgical castration. Methods A total of 69 patients with advanced prostate cancer treated by sur-gical castration completed the European organization for research and treatment of cancer quality of life questionnaire (QLQ-C30) and QLQ-prostate specific 25-item (PR25) module third at a 12-month interval.The assessment points were preoporative,6 months postoperative and 12 months postoperative. Results Although there were improvement on pain relief (P < 0.01 ) and symptom of urinary (P < 0.01 ) and global health (P < 0.01 ), the physical functioning (P < 0.05 ), role functioning (P < 0.01 ), emotional functioning (P < 0.01 ), cognitive functioning (P < 0.05 ), social functioning (P < 0.05 or < 0.01 ) were found significantly reduced , and insomnia (P < 0.05) and fatigue (P < 0.01 ) aggravated, treatment related symptoms (P <0.01 )appeared predominantly, especially deprivation of sexual functioning. Conclusion The surgical cas-tration when treating advanced

  8. Influência da castração e da idade de abate sobre as características subjetivas e instrumentais da carne de cordeiros Corriedale Effects of castration and slaughtering age on the subjective and instrumental characteristics of meat from Corriedale lambs

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    Eunice de Leon Rota

    2006-12-01

    Full Text Available Este trabalho foi realizado com o objetivo de avaliar o efeito da castração e da idade de abate sobre as características subjetivas e instrumentais da carne de cordeiros Corriedale criados em condições extensivas de pastagem natural. Foram utilizados 60 cordeiros machos (30 não-castrados e 30 castrados abatidos no ano de 2003, aos 120, 210 e 360 dias de idade, nos meses de fevereiro, maio e outubro, respectivamente. As avaliações da carne foram realizadas no músculo Longissimus dorsi. Pela análise da variância, verificou-se que não houve efeito da interação castração × idade de abate nas características estudadas. Foi encontrada significância para a idade de abate nas características subjetivas espessura de gordura de cobertura e marmoreio (os índices foram mais baixos nos animais mais velhos e em todas as características instrumentais avaliadas, principalmente maciez, que diminuiu com o aumento da idade de abate. O efeito da castração foi significativo somente no componente de cor L*. A qualidade da carne foi similar entre cordeiros Corriedale castrados e não-castrados criados extensivamente em pastagem natural, entretanto, a idade de abate influenciou a qualidade da carne, que foi melhor nos animais abatidos aos 120 dias.The objective of this trial was to evaluate the effects of castration and slaughtering age on subjective and instrumental characteristics of meat from Corriedale lambs raised on native pasture. Sixty male lambs (30 castrated and 30 intact slaughtered at 120, 210 and 360 days of age were used in this experiment. The Longissimus dorsi muscle was used for all meat evaluations and analysis. No significant castration × slaughtering age interaction was observed for the studied variables. A significant slaughtering age effect was found for meat fat thickness and marbling, which had lower scores in animals slaughtered at more advanced age as well as for all instrumental characteristics of the meat, mainly

  9. Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: A meta-analysis of published trials.

    Science.gov (United States)

    Roviello, Giandomenico; Sigala, Sandra; Danesi, Romano; Re, Marzia Del; Bonetta, Alberto; Cappelletti, Maria Rosa; Zanotti, Laura; Bottini, Alberto; Generali, Daniele

    2016-05-01

    Abiraterone acetate and orteronel are two CYP-17 inhibitors that have been studied in prostate cancer. They have shown relevant toxicities, including fluid retention/oedema, hypokalaemia, hypertension, liver function test abnormalities and cardiac events. The goal of this study was to determine the risk of special adverse events related to CYP- 17 inhibitor in patients with metastatic castration-resistant prostate cancer (CRCP). Summary data from four randomized phase III trials comparing CYP-17 inhibitors and prednisone versus placebo and prednisone in metastatic CRCP patients were meta-analysed. Pooled risk ratios (RRs) for the risk of all-grade and grade 3-4 adverse events of special interest were calculated. Data from 4916 patients (2849 in the AA experimental arm; 2067 in the control arm) were analysed. The incidence of grade 3-4 adverse events was never more than 10% of the patients. However, compared with placebo, the CYP-17 inhibitor significantly increased the all-grade events of hypertension (RR=1.53; 95% CI=1.3-1.8; pevents, hypokalaemia (RR=4.23; 95% CI=1.28-13.99; p=0.02) and cardiac disorders (RR=1.55; 95% CI=1.18-2.05; p=0.002). A lot of adverse events such as hypertension, hypokalaemia, cardiac disorders and liver function test abnormalities are increased during CYP-17 inhibitor based therapy. Strict monitoring of these side effects should be considered during CYP- 17 inhibitor therapy in prostate cancer patients.

  10. Effects of erzhibaihe extraction on the anxiety behavior of the female castrated rats%二至百合浓缩膏对去势雌性大鼠焦虑行为学的影响

    Institute of Scientific and Technical Information of China (English)

    靳冉; 翟建英; 岳枫; 张瀚涛; 陈霞; 刘丹; 李晋生

    2013-01-01

    目的探讨二至百合浓缩膏对去势雌性大鼠(双侧卵巢切除术)焦虑行为学的影响。方法3~4月龄Wistar雌性大鼠随机分成5组,假手术对照组,模型组,二至百合高、中、低剂量组。除假手术组,其余用手术摘除双侧卵巢建立去势更年期大鼠模型,给药组分别给予二至百合浓缩膏水溶液(1.92、0.96、0.48g/kg),假手术空白对照组和模型对照组给予相应容量的蒸馏水,连续45d。采用高架十字迷宫和明暗箱实验,观察实验大鼠行为学的变化。结果二至百合高剂量组可显著减低模型大鼠高架十字迷宫实验中OT%,与模型组比较差异有统计学意义(P<0.05)。二至百合高、中剂量组亦可显著升高大鼠明箱停留时间和穿箱次数,与模型组比较差异有统计学意义(均P<0.05)。结论二至百合浓缩膏具有较好的改善去势雌性模型大鼠焦虑症状的作用。%Objective To study the effects of Erzhibaihe extraction on the anxiety behavior of the female castrated rats. Methods 3-4 month-old female wistar rats were randomized into five groups with pseudo-operated group,model group,erzhibaihe high dose group, Medium dose group and low dose group. All rats were established the models of climacteric syndrome with ovariectomized surgical except pseudo-operated group. Treatment group were given Erzhibaihe extraction(1.92,0.96,0.48 g/kg)for 45 days, pseudo-operated group and model group rats were given corresponding volumes of distilled water.Then the elevated plus-maze test and light-dark transitions test were performed to observe behavior changes of rats. Results Compared with pseudo-operated group,the OE%(open arm entry percent)and OT%(open arm time percent)of model group rats were significantly reducedin the elevated plus-maze test.The OT% of Erzhibaihe high dose group were significantly reduced,and there were significantly differenceswith model group.In the light

  11. 去势后阻断自噬对大鼠前列腺细胞凋亡的影响%The influence of blocking autophagy to apoptosis in rat prostate after castration

    Institute of Scientific and Technical Information of China (English)

    凌生涛; 姚启盛; 柳建军; 陈从波; 黄力; 王黎

    2015-01-01

    Objectives To discuss the influence of blocking autophagy to apoptosis in rat prostate after cas-tration.Methods Seventy-two healthy male SD rats were randomly divided into 3 groups: the sham operation group, castration group and hydroxychloroquine group.Each group contains 24 rats.After 24 hours, 72hours, 7days, 10days, 14days and 21 days of the operation, we took out four rats randomly from each group and removed the protastes.Then we observed the morphological changes of the prostates through optical microscope and the changes of cytolysosomes and apoptotic bodies in the prostates by electronic speculum.Analyzed the expression of the proteins of P62 and Caspase-3 by immunohistochemistry.Results The prostate tissues shranked remarkably in the castrated rats.Cytolysosomes were observed through electronic speculum.The expressoin of Caspase-3 increased significantly ( P Autophagy protect protaste from apoptosis, and apoptosis would increase after dealing with choroquine, which would provide new therapies for drug-resistant prostate cancer.%目的:探讨去势后阻断自噬对大鼠前列腺细胞凋亡的影响。方法 SD雄性大鼠72只随机分为3组:即假切对照组、去势组、去势+硫酸羟氯喹处理组。各组大鼠分别于术后第1、3、7、10、14、21d随机抽取4只,完整取出前列腺组织。 HE染色观察大鼠前列腺组织形态学变化,电镜下观察前列腺微观结构、自噬和凋亡的变化,免疫组化SP法检测自噬受体蛋白P62和凋亡促进蛋白 Caspase-3在前列腺组织中表达。结果光镜下去势后大鼠前列腺体积逐渐缩小,腺上皮细胞逐渐萎缩,核染色加深,腺泡萎缩甚至闭塞,间质增生,加用羟氯喹处理后这一变化更加明显。电镜下观察去势后自噬小体的数量明显增加。免疫组化检测去势后自噬活性蛋白P62表达减弱,用羟氯喹处理后表达增强;凋亡促进蛋白 Caspase-3表达增强,用羟氯喹处

  12. Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants, and Akt in preclinical models: New hope for patients with castration resistant prostate cancer.

    Science.gov (United States)

    Thamilselvan, Vijayalakshmi; Menon, Mani; Thamilselvan, Sivagnanam

    2016-10-01

    Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR-independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC. In this study, we sought to determine whether carmustine and selenite in combination could induce apoptosis and inhibit growth of CRPC in-vitro and in-vivo. CRPC (22Rv1, VCaP, and PC-3) cell lines in culture and xenograft mouse were used. Combination of carmustine and selenite treatment significantly increased reactive oxygen species, apoptosis and growth inhibition in CRPC cells with down regulation of anti-apoptotic (Bcl-2 and Mcl-1) and proliferative proteins (c-Myc and cyclin-D1). This effect was associated with complete reduction of AR/AR-variants, AR-V7, PSA and significant induction of p27Kip1. Combination treatment substantially abolished phospho-Akt, phospho-GSK-3β, and anchorage-independent growth in AR-positive and AR-negative cells. Consistent with in-vitro results, combination treatment effectively induced apoptosis and completely inhibited xenograft tumor growth and markedly reduced AR/AR-variants, AR-V7, PSA, and Bcl-2 in xenograft tumors without causing genotoxicity in host mice. Individual agent treatment showed only partial effect. The combination treatment showed a significant synergistic effect. The present study is the first to demonstrate that the combination of carmustine and selenite treatment completely suppressed CRPC tumor growth by reducing AR/AR-variants and Akt signaling. Our findings suggest that the combination of carmustine and selenite could constitute a promising next-generation therapy for successful treatment of patients with CRPC. PMID:27198552

  13. Health Economics and Radium-223 (Xofigo®) in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Case History and a Systematic Review of the Literature

    Science.gov (United States)

    Norum, Jan; Traasdahl, Erik R.; Totth, Arpad; Nieder, Carsten; Olsen, Jan Abel

    2016-01-01

    Objectives: Prostate cancer (PC) is the most common cancer in Western countries. Recent advances in the treatment of metastatic castration resistant prostate cancer (mCRPC) have caused significant pressure on health care budgets. We aimed to exemplify this dilemma presenting an example, radium-223 (Xofigo®), and review the literature. Methods: A 74-year-old man diagnosed with mCRPC was referred to our department in October 2014 for radium-223 therapy. We faced the following dilemma: is radium-223 standard therapy? Is it cost-effective? Medline was searched employing the following search criteria: “radium-223”, “alpharadin”, “Xofigo” and “prostate”. Exclusion and inclusion criteria were applied. Guidelines and cost-effectiveness analyses were focused. We also searched the websites of ASCO, ESMO and ISPOR. The web was searched, using Yahoo and Google search engines, for Health Technology Assessments (HTAs). Results: 181 publications were identified in the Medline database. Only four studies included the word “cost”, three “economics” and none “budget” in heading or abstract. None of the publications were thorough of cost analysis (cost-effectiveness, cost-utility, cost-minimizing or cost-of-illness analysis). Six HTAs and eight national guidelines were identified. The cost per quality adjusted life years was indicated €80.000-94,000. HTAs concluded reimbursement being not recommendable or no ultimate statement could be made. One pointed towards a limited use with caution. Conclusion: Guidelines were based on data from randomized clinical trials (RCTs). Health economics was not considered when guidelines were made. Most HTAs concluded this therapy not cost-effective or there was insufficient data for final conclusions. Licensing and reimbursement processes should be run simultaneously. PMID:26573043

  14. A randomized non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer

    Science.gov (United States)

    Hussain, Maha; Rathkopf, Dana; Liu, Glenn; Armstrong, Andrew; Kelly, Wm. Kevin; Ferrari, Anna; Hainsworth, John; Joshi, Adarsh; Hozak, Rebecca R.; Yang, Ling; Schwartz, Jonathan D.; Higano, Celestia S.

    2016-01-01

    Background Cixutumumab, a human monoclonal antibody (HuMAb), targets the insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vascular endothelial growth factor receptor-2. A non-comparative randomized phase II study evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Men with progressive mCRPC during or after docetaxel therapy received mitoxantrone 12 mg/m2 on day 1 and prednisone 5 mg twice daily and were randomized 1:1 to receive either cixutumumab or ramucirumab 6 mg/kg intravenously weekly in a 21-day cycle. Primary endpoint was composite progression-free survival (cPFS). Secondary endpoints included safety, response, radiographic PFS, and overall survival (OS). Sample size was based on a 50% increase in median cPFS from 2.6 (MP) to 3.9 months (either combination). Results 132 men were treated (66 per arm). Median cPFS was 4.1 months (95% CI, 2.2–5.6) for cixutumumab and 6.7 months (95% CI, 4.5–8.3) for ramucirumab. Median time to radiographic progression was 7.5 months for cixutumumab and 10.2 months for ramucirumab, with a median OS of 10.8 and 13.0 months, respectively. Fatigue was the most frequent adverse event (AE). Incidence of most non-hematologic grade 3-4 AEs was <10% on both arms. Grade 3 cardiac dysfunction occurred in 7.6% of patients on ramucirumab. Conclusion Combinations of cixutumumab or ramucirumab plus MP were feasible and associated with moderate toxicities in docetaxel pretreated men with mCRPC. Of the two regimens, the ramucirumab regimen is worthy of further testing based on the observed cPFS relative to the historical control. PMID:26082390

  15. A phase I study of combined docetaxel and repeated high activity {sup 186}Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

    Energy Technology Data Exchange (ETDEWEB)

    Dodewaard-de Jong, Joyce M. van; Bloemendal, Haiko J. [Meander Medical Centre, Department of Internal Medicine, Amersfoort (Netherlands); Klerk, John M.H. de; Haas, Marie J. de [Meander Medical Centre, Department of Nuclear Medicine, Amersfoort (Netherlands); Bezooijen, Bart P.J. van [Meander Medical Centre, Department of Urology, Amersfoort (Netherlands); Wilson, Richard H.; O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, N. Ireland (United Kingdom)

    2011-11-15

    Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and {sup 186}Re-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity. A dose escalation schedule was designed consisting of four dose levels with a standard dosage of docetaxel (75 mg/m{sup 2} 3-weekly). {sup 186}Re-HEDP was given in increasing activities (1,250 MBq up to 2,500 MBq) after the third and sixth cycle of docetaxel. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to six if a DLT occurred. Fourteen patients were recruited with a median age of 64.6 years. One DLT, grade 3 thrombocytopenia lasting >10 days, occurred at dose level 3 leading to expansion of this group to six. One of these patients had an episode of acute renal failure which resolved. Because of production problems of {sup 186}Re-HEDP dose level 4 was not started. Combined therapy with docetaxel and {sup 186}Re-HEDP is generally well tolerated in patients with CRPC metastatic to bone. We will conduct a randomized phase II study using three cycles of docetaxel 75 mg/m{sup 2} 3-weekly followed by {sup 188}Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m{sup 2}, followed by {sup 188}Re-HEDP 20 MBq/kg body weight. (orig.)

  16. Research progress on the molecular signaling pathway of castration-resistant prostate cancer%去势抵抗性前列腺癌分子信号通路的研究进展

    Institute of Scientific and Technical Information of China (English)

    张秀娜; 赵伟; 高晓芳; 杨勇; 季晖

    2015-01-01

    在美国前列腺癌( PCa)是男性最常见的非皮肤性癌症以及癌症相关死亡的第二号杀手。雄激素与雄激素受体是前列腺癌的关键效应器,因此,雄激素剥夺治疗( ADT)是前列腺癌患者的一线治疗方法,并且效果良好,但是前列腺肿瘤最终复发并进展为去势抵抗性前列腺癌( CRPC)这一致命性形式。研究雄激素受体与去势抵抗性前列腺癌发生发展的关系及其可能的分子机制,可以为其临床诊断、治疗以及进一步的研究提供科学依据。%In United States,prostate cancer is the most commonly diagnosed non-cutaneous cancer in males and the second leading cause of cancer-related death for men. Androgen and the androgen receptor( AR)are critical effectors of prostate cancer. Consequently,androgen deprivation therapy( ADT)is typically employed as a first-line treatment for pros-tate cancer patients. While initial responses are generally positive,prostate tumors frequently recur and progress to a lethal form known as castration-resistant prostate cancer( CRPC). To study the relationship between androgen receptor and the initiation and development of CRPC,along with the possible molecular mechanisms,helps to diagnosis and treatment of cas-tration-resistant prostate cancer( CRPC),and provide the basis for further research.

  17. Co-targeting hexokinase 2-mediated Warburg effect and ULK1-dependent autophagy suppresses tumor growth of PTEN- and TP53-deficiency-driven castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-05-01

    Full Text Available Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC patients who have developed resistance to the second generation anti-androgen receptor (AR axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2-mediated Warburg effect with 2-deoxyglucose (2-DG and ULK1-dependent autophagy with chloroquine (CQ selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten−/p53-deficiency-driven CRPC mouse model. Mechanistically, 2-DG causes AMPK phosphorylation, which in turn inhibits mTORC1-S6K1 translation signaling to preferentially block anti-apoptotic protein MCL-l synthesis to prime mitochondria-dependent apoptosis while simultaneously activates ULK1-driven autophagy for cell survival to counteract the apoptotic action of anti-Warburg effect. Accordingly, inhibition of autophagy with CQ sensitizes cancer cells to apoptosis upon 2-DG challenge. Given that 2-DG is recommended for phase II clinical trials for prostate cancer and CQ has been clinically used as an anti-malaria drug for many decades, the preclinical results from our proof-of-principle studies in vivo are imminently translatable to clinical trials to evaluate the therapeutic efficacy by the combination modality for a subset of currently incurable CRPC harboring PTEN and TP53 mutations.

  18. A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

    Directory of Open Access Journals (Sweden)

    Carducci Michael

    2010-02-01

    Full Text Available Abstract Background To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA/interferon-alpha2b (IFN with paclitaxel (TAX, or mitoxantrone, estramustine and vinorelbine (MEV will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC. Methods 70 patients were treated with either MEV (Arm A in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B. Patients were assessed for response, toxicity, quality of life (QOL, and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC. Results The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d., and a significantly lower level of QOL than Arm A (p = 0.01. As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03. Conclusions Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy. Trial Registration Clinical Trials Registration number: CDR0000067865

  19. Clinical Observation of High Intensity Focused Ultrasound Combined with Radiotherapy、Testicular Castration for Prostate Cancer%高强度聚焦超声联合放疗、睾丸去势治疗前列腺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    唐勇军; 余建军; 冯慧萍

    2014-01-01

    目的:探讨高强度聚焦超声( HIFU)联合放疗、睾丸去势治疗前列腺癌的疗效。方法对38例已行放疗、睾丸去势治疗的前列腺癌进行HIFU治疗。结果15例(39%)前列腺特异性抗原(PSA)水平降至正常,20例(52%) PSA下降,2例(10%)仅症状缓解,有效率达92%。前列腺体积也明显缩小。结论 HIFU联合放疗、睾丸去势治疗前列腺癌,能有效控制肿瘤进展,为前列腺癌提供了1种新的有效治疗手段。%Objective To study the efficacy of high intensity focused ultrasound ( HIFU) combined with radiotherapy , testicular castration for prostate cancer .Methods 38 patients with prostate cancer who underwent radiotherapy and testicular castration were treated with HIFU.Results 15 cases (39%),prostate specific antigen (PSA) have fallen to normal,20 cases (52%) of the PSA declined,2 cases (10%) of symptoms relieved,effective rate was 92%.Prostate volume also narrowed con-siderably.Conclusion HIFU combined with radiotherapy and testicular castration can effectively control the progression of the tumor,it is a new effective treatment for prostate cancer .

  20. Características de carcaça e qualidade de carne de bovinos inteiros ou castrados da raça Nelore, suplementados ou não durante o primeiro inverno Carcass characteristics and meat quality of intact or castrated bovines, supplemented or not during the first winter

    Directory of Open Access Journals (Sweden)

    Saulo Malaguido Climaco

    2006-12-01

    Full Text Available Este trabalho teve como objetivo avaliar características quantitativas e qualitativas da carcaça e da carne de bovinos inteiros e castrados, suplementados ou não durante o primeiro inverno. Foram utilizados 40 bovinos Nelore, machos, inteiros e castrados, com peso inicial e idade média de 300kg e 14 meses, submetidos a dois tratamentos: SUP - os animais foram mantidos em pasto e receberam suplementação (0,5% do peso vivo constituída por 25% de farelo de soja e 75% de milho em grão triturado, durante o primeiro inverno (01/06/2003 a 21/09/2003; NSU- animais mantidos em pasto, sem suplementação. Após o abate, à idade média de 28 meses, foram avaliadas as características de carcaça. Os animais do tratamento NSU apresentaram maior (P0,05 quanto à espessura de gordura subcutânea entre animais inteiros e castrados (2,20 vs 4,17mm, respectivamente, porém os castrados apresentaram maior (PThis research was aimed at evaluating quantitative and qualitative characteristics of the carcass and meat from intact or castrated beef cattle, supplemented or not supplemented during the first winter. Forty Nellore males, intact or castrated, with initial weight and age of 300kg and 14 months, were submitted to the treatments: 1 SUP - Animals on pasture and supplemented (0.5% of the live body weight with concentrated (25% of soybean meal and 75% of ground corn during the first winter (06/01/2003 to 09/21/2003, and 2 NSU - Animals on pasture, without supplementation. At slaughter, on an average age of 28 months, the carcass characteristics were evaluated. Animals of the NSU treatment presented the largest (P0.05 for fat thickness between castrated and intact animals (4.17 vs 2.20 mm, respectively, however, castrated animals presented greater (P<0.05 fat percentage in the carcass (16.68 vs 11.34% and more tender meat (6.57 vs 7.50kgf than the intact animals. Intact and non-supplemented animals presented backfat thickness lower than required by the

  1. Características de carcaça e da carne de suínos machos castrados e imunocastrados alimentados com diferentes níveis nutricionais Carcass characteristics and meat of surgically castrated and immunocastrated pigs fed different nutritional levels

    Directory of Open Access Journals (Sweden)

    Eloiza Lanferdini

    2012-11-01

    Full Text Available O trabalho foi realizado para avaliar as características de carcaça e carne de suínos machos castrados e imunocastrados alimentados com dietas contendo diferentes níveis nutricionais. O delineamento experimental foi inteiramente casualizado com quatro tratamentos principais (T1-suínos machos castrados alimentados com dieta basal; T2-machos imunocastrados alimentados com dieta basal; T3-machos imunocastrados alimentados com dieta basal+3% aminoácidos e energia; T4-machos imunocastrados alimentados com dieta basal+5% aminoácidos e energia e dois tratamentos secundários com ou sem ractopamina dentro de cada tratamento principal. Os suínos machos castrados apresentaram peso de abate 3,3% inferior (PThe study was carried out to evaluate the carcass characteristics and meat of surgically castrated and immunocastrated pigs fed with different nutritional levels. The animals were distribuited in a completely randomized experimental design with four main treatments (T1-surgically castrated pigs fed with basal diet; T2-immunocastrated pigs fed with basal diet; T3-immunocastrated pigs fed with basal diet+3% amino acids and energy; T4-immunocastrated pigs fed with basal diet+5% amino acids and energy and two secondary treatments with or without ractopamine within each main treatment. The surgically castrated pigs had slaughter weight 3.3% lower (P<0.05, cold carcass weight 1.4% higher (P<0.05 and loin chop weight 13% higher (P<0.05 compared to immunocastred pigs. The immunocastrated pigs supplemented with 5% more amino acids and energy had rib 19% more heavier (P<0.05 and higher values (P<0.05 in the color b* (yellow-blue in the meat to 45min and 24h post-slaughter compared with surgically castrated pigs fed with basal diet. Supplementation with 5% amino acids and energy increases weight and yield of rib and changes the value of color b* (yellow-blue in the meat to 45min and 24h post-slaughter male pigs immunocastrated.

  2. Impact of Bone-targeted Therapies in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer Patients Treated with Abiraterone Acetate: Post Hoc Analysis of Study COU-AA-302

    Science.gov (United States)

    Saad, Fred; Shore, Neal; Van Poppel, Hendrik; Rathkopf, Dana E.; Smith, Matthew R.; de Bono, Johann S.; Logothetis, Christopher J.; de Souza, Paul; Fizazi, Karim; Mulders, Peter F.A.; Mainwaring, Paul; Hainsworth, John D.; Beer, Tomasz M.; North, Scott; Fradet, Yves; Griffin, Thomas A.; De Porre, Peter; Londhe, Anil; Kheoh, Thian; Small, Eric J.; Scher, Howard I.; Molina, Arturo; Ryan, Charles J.

    2016-01-01

    Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Intervention Patients were grouped by concomitant BTT use or no BTT use. Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy

  3. 阿比特龙联合泼尼松治疗去势抗拒前列腺癌的临床观察%Clinical Observation of Abriaterone Acetate and Prednison on Patients with Castration-resistant Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    许玉霞; 张华锋; 李长岭

    2015-01-01

    目的 探讨新型雄激素合成抑制剂醋酸阿比特龙(Abriaterone acetate)治疗去势抗拒前列腺癌(castration-resistant prostate cancer,CRPC)的疗效及安全性.方法 经病理证实并符合入选标准的58例去势抗拒前列腺癌患者,中位年龄68岁(61~81岁),接受醋酸阿比特龙治疗,化疗至少2周期后.按实体瘤疗效评价标准(RECIST)美国NCI制定的毒性评价指标(CTC-AE3.0)评价疗效和毒性反应;采用Kaplan-meier法对患者总生存时间(OS)进行分析.结果 5例未完成总评估过程.可评价疗效的53例患者中,总有效率(ORR) 18.87%(10例),疾病控制率(DCR) 62.26%(33例);中位OS为(15.0±1.2)月;28例前列腺特异性抗原(prostate-specific antigen,PSA)下降>50%,治疗前后PSA中位数分别为78 ng/ml(18~1 776 ng/ml)和37 ng/ml(9~320 ng/ml),两者比较差异有统计学意义(P<0.05);化疗不良反应多为Ⅰ~Ⅱ级.结论 阿比特龙联合泼尼松治疗去势抗拒前列腺癌疗效较好,不良反应轻.

  4. 甲状旁腺激素与雌激素对去势雌性大鼠牙槽骨代谢的影响%Influence of parathyroid hormone and estrogen on alveolar bone metabolism of castrated female rats

    Institute of Scientific and Technical Information of China (English)

    孙哲; 林志勇; 白广亮; 狄婧; 姜丽霞

    2014-01-01

    Objective To investigate the influence of parathyroid hormone and estrogen on alveolar bone metabolism of castrated female rats. Methods Sixty-six female Wistar rats which were healthy and 4 months old were divided into two groups, with group SHAM (n=18) and group ovariectomy (OVX) (n=48). After 8 weeks of ovariectomy, the osteoporosis model was confirmed by examing 8 ovariectomized and sham-operated rats. The rest 10 rats in group SHAM were the control group (group A). The rest 40 rats in group OVX were divided into ovariectomized group (group B), ovariectomized and treated with estrogen (group C), ovariectomized and treated with parathyroid hormone (group D), ovariectomized and treated with estrogen and parathyroid hormone (group E) at random with 10 in each group. Group A and B injected physiological saline (1 mL·kg-1), group C injected estradiol benzoate (10 μg·kg-1), group D injected parathyroid hormone (20 μg·kg-1), group E injected parathyroid hormone (20 μg·kg-1) and estradiol benzoate (10 μg·kg-1). The intraperitoneal injection were maken every other day to rats in each group, which continued for 8 weeks. The bone mineral density (BMD), bone histomorphology and serum Ca, P, alkaline phosphatase (ALP) were measured after therapy. Results After 8 weeks of ovariectomy, the lumbar BMD of ovariectomized rats were significantly declined compared with those of the sham-operated rats (P0.05). ALP values in group B was significantly higher than that in group A (P0.05),B组ALP值较A组明显升高(P<0.05)。结论间歇性、小剂量注射甲状旁腺激素能增加去势大鼠牙槽骨的骨密度和改善骨结构,与雌激素联合使用对骨质疏松的治疗有协同作用。

  5. Contenido de glicosaminoglicanos del líquido sinovial de la articulación metacarpofalángica de caballos castrados y yeguas de diferentes edades Synovial fluid glycosaminoglycan concentration in metacarpophalangeal joint of castrated horses and mares of different ages

    Directory of Open Access Journals (Sweden)

    H. ADARMES

    2003-01-01

    Full Text Available Se midió la concentración de glicosaminoglicanos (GAGs del líquido sinovial en su valor total (GAGsT y de una fracción de éstos, que corresponde a los GAGs diferentes del ácido hialurónico o GAGs sulfatados (GAGsS, entre los que se describen condroitin sulfato y queratán sulfato. Las muestras de líquido sinovial se obtuvieron por artrocéntesis aséptica desde articulaciones metacarpofalángicas normales de equinos mestizos en matadero, después del beneficio de los animales. El exámen post mortem de las articulaciones permitió descartar articulaciones con evidencias de osteoartritis u otras patologías articulares. La normalidad del líquido sinovial se evaluó por de su aspecto y por las pruebas del coágulo de mucina y de concentración de proteínas (Total concentration of synovial fluid glycosaminoglycan (GAGs and a fraction of it (GAGsT which correspond to different GAGs from hyaluronic acid or sulfated GAGs (GAGsS that mainly consist of chondroitin sulfate and keratan sulfate, were measured. Samples of synovial fluid were taken from normal metacarpophalangeal joints of crossbred equines immediatelly after slaughter by aseptic needle aspiration. Post mortem joints examination showed that there was no gross evidence of osteoarthritis or other joint disease, based on the appearance of synovial membrane and articular cartilage. Synovial fluid samples were evaluated by its external appearance, protein concentration and mucin clot test. Samples were alloted in four age groups by teeth examination and divided in mares (m and castrated horses (c.h. as follows: 1.5 - 2 years (n = 23: 12 m. and 11 c.h.; 4 - 5 years (n = 15: 9 m. and 6 c.h.; 6 - 8 years (n = 23: 13 m. and 10 c.h. and over 10 years old (n = 17: 12 m. and 5 c.h.. A colorimetric method with Alcian Blue using different electrolyte concentrations was used to quantify these GAGs. There were no significant differences of GAGsT concentration between mares and castrated horses

  6. Acupuncture Castrated Rabbit Dry Eye Model Schirmer and Related proteins of the Lacrimal Gland Epithelial Cells Fas / FasL Expression%针刺对去势雄兔干眼模型泪液分泌及泪腺上皮细胞相关蛋白Fas/FasL表达的影响

    Institute of Scientific and Technical Information of China (English)

    张月梅; 高卫萍

    2012-01-01

    目的:探讨针刺对去势雄兔干眼动物模型泪液分泌及泪腺上皮细胞凋亡相关蛋白Fas、FasL表达的影响.方法:健康成年雄兔18只,随机分为正常组、干眼组和针刺组,每组6只.干眼组和针刺组行双侧睾丸及附睾切除制作干眼模型,2周后去势雄兔干眼模型形成并稳定后对针刺组进行局部针刺,各组兔分别于去势前和去势后1、2、3、4、5、6、7周检测泪流量,并对各组兔泪腺进行免疫组化研究.结果:针刺2周后针刺组泪液分泌增加,与干眼组相比差异有统计学意义(P<0 05).7周后,对各组兔泪腺进行免疫组化,干眼组泪腺上皮细胞Fas、FasL表达明显高于针刺组,差异具有统计学意义(P<0.05),针刺组与正常组没有统计学差异(P>0.05).结论:局部针刺能够抑制凋亡的发生,增加去势干眼雄兔泪液的分泌.%Objective: This article is to study the effect of acupuncture on tear secretion, and lacrimal gland epithelial pathological apoptosis-related proteins' Fas/FasL of castrated male rabbits animal models with dry eye symptoms. Methods: Divide 18 healthy adult male rabbits randomly into normal group, dry eye group and acupuncture group ( 6 rabbits each group ) . Do bilateral removal of the testis and epididymis on dry eye group and acupuncture group to produce dry eye models. After 2 weeks, do local acupuncture treatment on castrated male rabbits when the dry eye model formed and became stable. Test tears flow of each group of rabbits before castration and 1 ,2,3,4,5,6,7 weeks after castration. Take rabbit lacrimal glands of each group for immunohistochemical study. Results: After 2 weeks of acupuncture, tear secretion of acupuncture treatment group increased, and the result is statistically significant ( P0.05 ) .Conriusion : Local acupuncture can inhibit the occurrence of apoptosis, increase castration dry eye the secretion of tears the rabbit.

  7. Voluntary chemical castration of a mental patient.

    Science.gov (United States)

    Brahams, D

    1988-06-01

    Britain's High Court recently overruled two decisions of the Mental Health Act Commission that denied certification of a voluntary experimental drug treatment to a mental patient, holding that the standard for informed consent is determined not by the subjective judgment of the commissioners but by whether the patient knows the nature and likely effects of treatment and that its use in his case is a novel one. The background facts of the case involving a 27-year-old pedophile receiving goserelin implantations to reduce testosterone levels are presented and the issues of jurisdiction under the Mental Health Act 1983 and the commissioners' duty to act fairly and to consider the likely benefits of treatment are discussed. PMID:2897553

  8. Voluntary chemical castration of a mental patient.

    Science.gov (United States)

    Brahams, D

    1988-06-01

    Britain's High Court recently overruled two decisions of the Mental Health Act Commission that denied certification of a voluntary experimental drug treatment to a mental patient, holding that the standard for informed consent is determined not by the subjective judgment of the commissioners but by whether the patient knows the nature and likely effects of treatment and that its use in his case is a novel one. The background facts of the case involving a 27-year-old pedophile receiving goserelin implantations to reduce testosterone levels are presented and the issues of jurisdiction under the Mental Health Act 1983 and the commissioners' duty to act fairly and to consider the likely benefits of treatment are discussed.

  9. Reviews on Abiraterone Acetate Treatment on Metastatic Castration-Resistant Prostate Cancer%醋酸阿比特龙治疗转移性去势抵抗性前列腺癌综述

    Institute of Scientific and Technical Information of China (English)

    陈文东; 孙艳; 王沭; 杜芬

    2016-01-01

    Advanced prostate cancer (PCa) eventually progresses to castrate-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) because the adrenal and prostate cancer cells still generate androgen that stimulates the growth of tumor cells. Abiraterone acetate is a specific inhibitor of CYP17 that blocks testicular, adrenal and tumor androgen biosynthesis. Large phase III randomized clinical trials have proved that abiraterone acetate improved overall survival, delayed disease progress, controlled disease-related symptoms, and improved quality of life in metastatic CRPC (mCRPC) patients without chemotherapy or with failed chemotherapy. The published economic analysis suggested that the combination of abiraterone and low dose prednisone was cost-effective compared with other new therapies in post-chemotherapy mCRPC patients. Additionally, abiraterone acetate was found to have minimal budget impact on health plans likely due to small size of patients and saved health resources utilization associated with administration and safety of abiraterone acetate. The treatments for mCRPC in China are limited and the launch of using abiraterone acetate provided patients and health care providers a new treatment option.%经雄激素剥夺疗法(ADT)治疗后,晚期前列腺癌(PCa)最终进展为去势抵抗性前列腺癌(CRPC)的原因是睾丸外器官(肾上腺)和前列腺癌细胞本身仍有合成雄激素的能力,继续刺激癌细胞的生长。醋酸阿比特龙是CYP17酶的选择性抑制剂,能全面阻断睾丸、肾上腺和前列腺癌细胞中的雄激素生物合成。大型三期随机对照临床试验均已证明,对未经化疗或者化疗失败的转移性CRPC(mCRPC)患者,醋酸阿比特龙联合小剂量泼尼松能够显著提高患者生存时间、延缓疾病进展、缓解疾病症状、提高患者生命质量。已发表的经济学分析表明,在化疗后的人群中,阿比特龙方案相对于其

  10. 杜仲叶对去势骨质疏松大鼠骨代谢的影响%Effect of eucommia ulmoides oliv leaves on bone metabolism in castrated osteoporotic rats

    Institute of Scientific and Technical Information of China (English)

    戴鹏; 邓鸣涛; 张立超; 朱美兰; 林思俭; 刘荣华; 罗军

    2012-01-01

    showed relative increases in BMD and smooth joint surface. Histopathology showed normal bone trabecular number. Biochemical tests showed that the levels of bone alkaline phosphatase, serum calcium, serum phosphorus, urinary calcium, and urinary phosphorus had no significant difference with those in normal control group. Conclusion Eucommia ulmoides oliv leaves can maintain bone metabolic balance, and prevent and treat osteoporosis in castrated rats. The effect is mainly on the increase of BMD, the increase of bone trabecular number, and the improvement of bone metabolic balance.

  11. Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5α-reductase inhibitor%去势或用5α-还原酶抑制剂后雄性大鼠血管内皮超微结构改变的研究

    Institute of Scientific and Technical Information of China (English)

    Y. L. Lu; L. Kuang; H. Zhu; H. Wu; X. F. Wang; Y. P. Pang; N. J. Wang; D. L. Yu

    2007-01-01

    Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods:Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P < 0.01);DHT concentrations of group D rats were significantly decreased (P < 0.01) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces,which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.%目的:研究低雄性激素水平对雄性大鼠血管内皮超微结构改变的影响.方法:将48只雄性SD大鼠随机分成四组:A组为正常大鼠作为对照组,B组为雄性大鼠去势组,C组为去势后用十一酸睾酮(T)替代治疗大鼠组,D组为正常大鼠用5α-还原酶抑制剂治疗组,每组均为12只大鼠.10周后用放射免疫法测定血清睾酮,游离睾酮(Free Testosterone,FT)和双氢睾酮(Dihydrotestosterone,DHT)水平,用扫描电镜观察大鼠腹主动脉内皮的超微结构并给予血管内皮结构评分(VESS).结果:B组的血清睾酮和游离睾酮的水平与A、C、D组相比较有显著地降低(P<0.01);D组的双氢睾酮水平与A组和C组比较显著地降低(P<0.01);

  12. Desempenho de cordeiros inteiros ou submetidos a diferentes métodos de castração abatidos aos 30 kg de peso vivo Performance of intact or submitted to different methods of castration lambs slaughtered at 30 kg of live weight

    Directory of Open Access Journals (Sweden)

    Edson Luis de Azambuja Ribeiro

    2003-06-01

    Full Text Available Foram utilizados neste experimento 31 cordeiros cruzados Hampshire Down, Ile de France e Suffolk, distribuídos em quatro tratamentos: inteiros ou castrados com burdizzo, borracha ou faca. A castração ocorreu aos 58 dias de idade. Após o desmame, aos 84 dias, os animais foram confinados até atingirem o peso vivo de 30 a 32 kg, quando abatidos. Não houve diferença significativa entre os tratamentos e entre os grupos genéticos para os pesos ao nascimento, desmame e abate, para o ganho de peso médio diário do nascimento ao abate e para a idade ao abate. As médias para os ganhos de peso foram 0,179; 0,177; 0,170 e 0,147 kg e para a idade ao abate de 152,0; 156,0; 161,5 e 188,9 dias para os cordeiros inteiros, castrados com burdizzo, com borracha e com faca, respectivamente. Os cordeiros Hampshire Down, Ile de France e Suffolk ganharam, respectivamente, 0,176; 0,163 e 0,166 kg diariamente. Os animais inteiros apresentaram menores rendimentos verdadeiros de carcaça quente ou fria; não havendo outras diferenças importantes entre os tratamentos para as demais características de carcaça estudadas. Os cordeiros Hampshire Down apresentaram maiores rendimentos de carcaça fria, enquanto os Suffolk tiveram menores rendimentos verdadeiros de carcaça e menor percentagem de pescoço, e os Ile de France apresentaram as carcaças mais curtas. O peso ao nascimento teve efeito significativo sobre o ganho de peso e a idade ao abate dos cordeiros. Os resultados mostraram não haver diferenças no desempenho de cordeiros inteiros ou castrados por diferentes métodos abatidos entre 30 e 32 kg de peso vivo, e que pode ocorrer diferenças entre animais de diferentes grupos genéticos quando abatidos com peso semelhante.Thirty-one Hampshire Down, Ile de France and Suffolk crossbred lambs divided into four treatments: intact, castrated with burdizzo, with rubber bands and with knife, were used in this experiment. Castration occurred at 58 days of age. After

  13. Reflections on the therapeutic use of {sup 223}RaCl{sub 2} for bone metastases resulting from prostate cancer resistant to castration; Reflexiones sobre el uso terapeutico de {sup 223}RaCl{sub 2} para metastasis osea derivada de cancer de prostata resistente a la castracion

    Energy Technology Data Exchange (ETDEWEB)

    Astudillo V, A. J.; Paredes G, L., E-mail: armando.astudillo@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2015-10-15

    In January 2014 the Comision Federal para la Proteccion contra Riesgos Sanitarios of the Ministry of Health in Mexico, authorize the use of {sup 223}RaCl{sub 2} as the first radiopharmaceutical emitter α for therapeutic purposes in cases of bone metastases resulting from prostate cancer resistant to castration. The paper analyzes the main variables that affect the metrological traceability using activity meters to evaluate the gamma activity of {sup 223}RaCl{sub 2} in hospitals, because it has a chain of complex decay with alpha, beta and gamma emitters, so was important to verify if a gamma activity measurement for a multiple emitter is reliable to determine the total alpha absorbed dose to bone in a patient. (Author)

  14. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    Science.gov (United States)

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  15. Comparison of the effects of surgical and drug castration on the psychology and quality of life in patients with prostate cancer%手术去势与药物去势对前列腺癌患者心理及生活质量影响的比较

    Institute of Scientific and Technical Information of China (English)

    周小波; 叶志弘; 郭丹红; 朱双爱; 蒋燕; 傅素靓; 张璟; 戚海琴; 刘娟

    2015-01-01

    Objective To study the effects of surgical castration and drug castration (androgen deprivation therapy) on the psychology and quality of life in patients with prostate cancer. Methods The symptom self rating scale (SCL-90), QLQ-C30 scale and QLQ-PR25 sub scale were used to investigate 102 cases of prostate cancer who accepted surgical cas-tration and 86 cases of prostate cancer who received androgen deprivation therapy before treatment and after treatment for 6 months and 12 months. Results The SCL-90 survey showed that the somatization, compulsion, interpersonal relation-ships, anxiety and psychotic after treatment for 6 months and 12 months of patients treated with two different therapies were significantly improved (t=2.87, 3.91, 3.49, 4.17, 1.99, 3.01, 3.95, 3.74, 4.28, 4.58; 2.09, 2.21, 2.17, 1.99, 3.96, 1.99, 2.13, 2.08, 1.99, 3.73,P<0.05). The two treatments relieved pain and improved urination after treatment for 6 and 12 months (t=3.76,4.51,3.51,4.58; 2.41,4.37,2.53,4.63,P<0.05), especially improving sexual function after treatment for 6 months(t=3.57,3.37,P<0.05). The treatment of medical castration had different degrees of improvement on sexual function, and surgical treatment caused permanent loss of sexual function. Conclusion Two kinds of treatment programs bring different psychological problems so that lower the quality of life. But the effect of medical castration on the quality of life of the patients is reversible.%目的 研究手术去势和药物去势即雄激素阻断治疗对前列腺癌患者心理及生活质量的影响.方法 采用症状自评量表(SCL-90)、癌症患者生命质量测定量表(QLQ-C30)及前列腺癌患者生活质量子量表(QLQ-PR25)对102例接受手术去势治疗和86例接受雄激素阻断治疗的前列腺癌患者,分别在治疗前、治疗后6个月及治疗后12个月的心理及生活质量状况进行评价. 结果 SCL-90显示两种治疗方法组在治疗6月后和治疗12月后躯体化、强迫

  16. Rendimentos de carcaça, dos cortes comerciais e da porção comestível de bubalinos Murrah castrados abatidos com diferentes períodos de confinamento Yields of carcass, retail cuts and retail beef cuts of castrated Murrah buffaloes slaughtered at different periods of feedlot

    Directory of Open Access Journals (Sweden)

    Paulo Francisco Nogueira Bomfim Ferreira Menegucci

    2006-12-01

    Full Text Available Avaliaram-se as características de carcaça de búfalos Murrah castrados terminados em confinamento. Foram utilizados 20 bubalinos Murrah (15 meses de idade e peso inicial de 207 kg, castrados e descornados, divididos em quatro grupos homogêneos e abatidos aos 75, 100, 125, 150 dias de confinamento, após período de adaptação. Ao abate, as carcaças foram identificadas, resfriadas por 24 horas para pesagem e cálculo dos rendimentos das meias-carcaças, dos cortes dianteiro, ponta-de-agulha, traseiro total e serrote. Não houve diferença estatística para o rendimento de carcaça. Os pesos de traseiro total, serrote e dianteiro apresentaram aumento linear, porém, observou-se efeito cúbico do período de confinamento sobre os rendimentos de traseiro total e dianteiro. Verificou-se ainda aumento linear dos pesos de filé-mignon, contrafilé, fraldinha, coxão mole, coxão duro, lagarto, sebo, porção comestível e ossos. O período de confinamento promoveu efeito linear decrescente sobre os rendimentos de patinho, músculo traseiro e maminha + alcatra e linear crescente para fraldinha e sebo.The objective of this trial was to evaluate the carcass traits of feedlot castrated Murrah buffaloes. Twenty castrated hornless Murrah buffaloes averaging 15 months of age and initial body weight of 207 kg were used. Animals were divided in four groups and slaughtered at 75, 100, 125 or 150 days of feedlot after an adaptation period. At slaughter, carcasses were identified, cooled for 24 hours, and weighed for calculation of yields of half carcass, hindquarter, spare ribs, forequarter, and sawcut. There was no significant difference for carcass yield comparing the different periods of feedlot. Weights of sawcut, forequarter, hindquarter, tenderloin, strip loin, thin skirt, topside, outside flat, eye round, tallow, retail beef cuts, and bones all increased linearly while significant cubic effects were observed for yields of forequarter and hindquarter

  17. Ameliorative effect of androgen therapy tear on film stability in castrate female rats%雄激素疗法对去势雌性大鼠泪膜稳定性的改善作用

    Institute of Scientific and Technical Information of China (English)

    高阳; 周瑾; 孙晓芳

    2015-01-01

    concentration was (3.38±0.24) ng/ml,S Ⅰ t was (6.37 ±0.45) mm/5 minutes and BUT was (7.54±0.55) seconds in the testosterone-injected group,which was significantly higher than that in the OVX model group (all at P =0.000).The positive staining of MUC5AC in rat conjunctival tissue weakened in the OVX model group compared with the normal control group,and the fluorescence intensity in the testosterone-injected group was stronger than that in the OVX model group.Regularly arranged microvilli and cell metabolism hiatus on the surface of corneal cells were seen in the normal control group and the sham group;while the microvilli were shorter and irregularly arranged,and the cell metabolism hiatus were disappeared in the OVX model group.However,microvilli and cell metabolism hiatus were close to normal ones in the testosterone-injected group.Conclusions Deterioration of tear secretion and instability of tear film are are probably associated with the lower serum androgen levels in castrated female rats.Systemic supplement of androgen can promote tear secretion,improve tear film stability and alleviate ocular surface damage.%背景 绝经期女性干眼的发病率明显高于男性,提示性激素在干眼的发病过程中可能发挥一定的作用,绝经期女性应用雌激素时于眼症状加重也提示雄激素可能参与干眼病程.雄激素的应用是否可以减轻干眼症状正在受到关注. 目的 探讨雄激素对去卵巢雌鼠泪液及泪膜稳定性的影响,探讨雄激素维持泪膜稳定性的可能作用机制. 方法 清洁级3月龄雌性性成熟Wistar大鼠48只按照随机数字表法分为正常对照组、假手术组、去势模型组和丙酸睾丸酮组,去势模型组和丙酸睾丸酮组大鼠行双侧卵巢摘除术以制备去势模型,造模后5同始丙酸睾丸酮组大鼠按3.75 mg/kg剂量肌内注射丙酸睾丸酮,每3天1次,持续6周,而假手术组大鼠仅切除腹内脂肪组织而不摘除卵巢.于丙

  18. 白膜下睾丸实质剜除术与药物去势治疗Ⅳ期前列腺癌疗效回顾性研究%Retrospective study of therapeutic efficacy of subcapsular orchiectomy and medical castration in prostate cancer patients-Ⅳ

    Institute of Scientific and Technical Information of China (English)

    赖彩永; 陈洁; 徐谊朝; 傅全胜; 张燊; 刘玉峰; 邹自灏; 黄伟佳; 蒋光愉; 苏泽轩; 李立; 李红; 梁蔚波; 卓育敏; 郭泽雄; 李宇同

    2012-01-01

    目的 回顾性分析白膜下睾丸实质剜除术与药物去势治疗Ⅳ期前列腺癌的疗效及副作用的差异.方法 2005年01月~2011年10月采用白膜下睾丸实质剜除术(n=70)和诺雷德联合康士得(n=62)治疗Ⅳ期前列腺癌并进行随访,分析其肿瘤缓解时间、总生存时间、手术并发症及对患者心理的影响.结果 随访时间1~59个月,手术组和药物组肿瘤缓解时间分别为18个月和17个月,两组差异无显著性(x2=0.166,P=0.682),总生存时间分别为33个月和31个月,两组差异无显著性(x2=0.080,P=0.778).手术组发生术后并发症的比率为10%,没有出现因睾丸切除导致的心理疾病.结论 白膜下睾丸实质剜除术作为Ⅳ期前列腺癌白膜下睾丸实质剜除方法,具有疗效确切、对心理影响少及成本低的特点,可作为Ⅳ期激素依赖型前列腺癌去势治疗的首选方法.%[Objective] To explore retrospectively the difference of therapeutic efficacy and side effect between subcapsular orchiectomy and medical castration in prostate cancer Patients-IV. [Methods] In the retrospective study, 132 consecutive Patients-IV were evaluated, the operation group (n =70) had primarily been treated by subcapsular bilateral orchiectomy and the medicine group (n =62) had received medical castration from Jan 2005 ~Oct 2011. Response to therapy, time of tumor remission, overall survival time, psychological disorders due to loss of organ and postoperative surgical complications were recorded. [ Results ] The follow up time was 1 -59 months. Median time of tumor remission of the operation group and medicine group were 18 and 17 months. The difference was sta tistically insignificant (x2=0.166, P =0.682). Median times of overall survival were 33 and 31 months respectively. The difference was statistically insignificant (x2=0.080, P =0.778). 10% of the operation group showed minor postoperative complications. No psychological disease occurred following

  19. Redução da proteína bruta da ração para suínos machos castrados dos 15 aos 30 kg mantidos em termoneutralidade Reduction of crude protein level of ration to castrated swine from 15 to 30 kg maintained in a termoneutral environment (22ºC

    Directory of Open Access Journals (Sweden)

    Rony Antonio Ferreira

    2003-12-01

    Full Text Available Um experimento foi conduzido para avaliar a influência da redução da proteína bruta (PB e suplementação de aminoácidos sintéticos sobre o desempenho de suínos machos castrados mantidos em ambiente termoneutro (22ºC. Foram utilizados 60 leitões mestiços (Landrace x Large White com peso médio inicial de 15,0 kg e idade média de 53,1 dias, em delineamento inteiramente ao acaso, com cinco tratamentos (18, 17, 16, 15 e 14% PB, seis repetições e dois animais por unidade experimental. As rações experimentais foram fornecidas à vontade até o final do experimento, quando os animais atingiram o peso médio de 30,2 kg. A temperatura média no interior da sala foi mantida em 22ºC, com umidade relativa de 82,3%. O Índice de Temperatura de Globo e Umidade calculado no período foi de 69,6. Não se observou efeito da redução do nível de proteína bruta da ração sobre as variáveis de desempenho (consumo de ração, ganho de peso e conversão alimentar. As taxas de deposição de proteína e gordura também não foram influenciadas pela redução da PB na ração. Os tratamentos influenciaram os pesos absoluto e relativo do estômago e o peso absoluto do intestino, sendo os maiores valores observados em animais que receberam a ração com maior nível de proteína bruta. Concluiu-se que o nível de PB da ração pode ser reduzido de 18 para 14%, sem prejudicar o desempenho de suínos machos dos 15 aos 30 kg mantidos em ambiente termoneutro, desde que devidamente suplementadas com aminoácidos essenciais limitantes.One experiment was conducted to evaluate the influence of reduction of the crude protein (CP level of ration with amino acid supplementation on performance of castrated males swines maintained in a termoneutral environment (22ºC. A total of sixty crossbred swines (Landrace x Large White, with average initial weight of 15.0 kg and 53.1 days old, was allotted to a completely randomized design with five treatments (18, 17, 16

  20. Development in the study of radium-223 chloride for treating castration-resistant prostate carcinoma with bone metastases%镭-223氯化物治疗去势抵抗性前列腺癌骨转移的研究进展

    Institute of Scientific and Technical Information of China (English)

    桂继琮; 刘兴党

    2015-01-01

    近年来,全世界前列腺癌的发病率和病死率不断增长,各种治疗方法的研究也进展迅速。镭-223发射的重α粒子(具有<100μm的超短波)靶向作用于骨转移部位和周围新骨生长区域。镭-223氯化物在药物临床试验中以稳定的安全性显著降低了患者的病死率,成为近来被寄予厚望的转移性去势抵抗性前列腺癌(CRPC)治疗领域的“主角”。2013年美国食品药品管理局已批准镭-223氯化物用于治疗有症状的骨转移、未发现内脏转移的CRPC患者。未来其联合治疗方案将会是研究的重点。%Prostate carcinoma rates and mortalities are increasing worldwide. The therapeutic landscape of castration-resistant prostate carcinoma (CRPC) has changed rapidly. Radium-223 chloride, which is a radiopharmaceutical agent, targets bone metastasis by emitting high-energy alpha-particles with extremely short range (<100 μm ) . This chemical is effective in reducing mortality without increasing toxicity. Thus, this agent has the potential to become a new alternative for treating patients with CRPC. The Food and Drug Administration approved radium-223 dichloride for treating patients with CRPC, symptomatic bone metastases, and unknown visceral metastatic disease in 2013. Therefore, combination and sequencing strategies will be future research directions.

  1. Effect of androgen on neuronal nitric oxide synthase and endothelial nitric oxide synthase in corpus cavernosum of castrated rats%雄激素对大鼠阴茎海绵体中神经型和内皮型一氧化氮合酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱家亮; 姜华茂; 候铁汉; 刘宇; 王海鹏

    2013-01-01

    目的 观察不同雄激素水平大鼠与大鼠海绵体神经型一氧化氮合酶(nNOS)和内皮型一氧化氮合酶(eNOS)表达的关系,探讨其临床意义.方法 选取40只SD雄性大鼠,随机分为正常对照(NC)组10只,去势组30只,常规去势造模后分别于接受不同浓度的十一酸睾酮灌胃(20、10 mg/kg)和生理盐水灌胃.4周后,采用免疫组织化学和Western blot法检测各组阴茎海绵体组织中nNOS和eNOS的表达.结果 NC组阴茎海绵体中nNOS和eNOS的表达量分别为98.24 ±3.02、80.04±2.96;1组的表达分别为92.81 ±3.37、78.75±4.02;2组的表达分别为45.70±3.83、75.68±5.36;3组的分别为20.24±4.06、71.64±3.04,结果显示去势组nNOS表达比NC组有明显的降低,在补充雄激素后恢复,而eNOS表达各组间差异无统计学意义(P>0.05).结论 eNOS的表达是非雄激素依赖性的,而nNOS的表达是雄激素依赖性的,推测雄激素主要通过nNOS途径来调控阴茎平滑肌的舒张.%Objective To investigate the effect of different androgen levels on neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in corpus cavernosum of castrated rats.Methods Forty Sprague-Dawley male rats were randomly divided into sham operated group (n =10) and operated group (n =30).The rats in operated group were castrated and divided into 3 subgroups:subgroups 1 and 2 were treated with high dose (20 mg/kg) or low dose (10 mg/kg) testosterone undecanoate respectively each day,and subgroup group 3 was given normal saline.After 4 weeks of treatment,the rats in each group were sacrificed for detection of nNOS and eNOS by immunohistochemistry and Western blotting.Results nNOS and eNOS protein expression was detectable in the penis tissue of all rats.The nNOS and eNOS expressin levels in sham operated group were 98.24 ± 3.02 and 80.04 ± 2.96,92.81 ± 3.37 and 78.75 ±4.02 in subgroup 1,45.70 ±3.83 and 75.68 ±5.36 in subgroup 2,and 20.24 ±4.06 and 71.64 ± 3

  2. 去势联合高强度聚焦超声治疗晚期前列腺癌对患者生存及免疫状态的影响%The influence of castration in combination with high intensity focused ultrasound treatment on survival and immune state of patients with advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    武睿毅; 王国民; 徐磊; 徐叶青

    2012-01-01

    Objective: To explore the influence of castration in combination with high intensity focused ultra-sound(HIFU) treatment on survival and immune state of patients as local therapy for advanced prostate cancer. Method:Between March 2000 and December 2010, we performed a prospective,controlled,and nonrandomized stud-y on 64 patients with advanced PCa after hormonal therapy. 30 cases in control group received hormonal therapy a-lone.and 34 cases in H1FU group received HIFU treatment following castration. To make survival analyses by the method of Kaplan-Meier survival curves and calculating survival rates. Some patients(control group 11 cases, HIFU group 12 cases)were detected the immunity index of peripheral blood before and after treatments, including IL-2, IFN-γ. VEGF,TGF-β1 and CD4 + CD25+ Foxp3+ cell. Result:The 3-year and 5-year survival rates of control group were 45. 19% and 25. 83%.and those of HIFU group were 76. 92% and 51. 26%. There was significant difference between two groups in survival curve( P =0. 0404). Compared with control group,IL-2( P =0. 042)and IFN-γ( P = 0. 019)level of peripheral blood in HIFU group significantly rose,and VEGF( P =0. 032) ,TGF-β1( P =0. 042) level and CD4+ CD25+ Foxp3+ ( % ) ( P =0. 001) significantly decreased. Conclusion: After castration treatment for advanced prostate cancer,combination with HIFU to strengthen local control of primary lesions could enhanced the therapeutic response of patients to hormone therapy, also improved systemic immune state, significantly prolonged the survival time of patients.%目的:探索晚期前列腺癌(prostate cancer,PCa)去势后,联合高强度聚焦超声(HIFU)局部治疗原发灶对患者生存和免疫状态的影响.方法:我院于2000年3月~2010年12月对64例晚期PCa去势手术后的患者进行前瞻性对照非随机研究,对照组30例接受单纯内分泌治疗,HIFU组34例去势后联合HIFU治疗.绘制两组患者的Kaplan-Meier生存曲线和并计算生存

  3. 阉割对金华猪肝脏miR-122和miR-378表达量和膻味性状的影响%Effect of Castration on the Boar Taint and the Expression Variation of miR-122 and miR-378 in Liver of Jinhua Pig (Sus scrofa)

    Institute of Scientific and Technical Information of China (English)

    马义涛; 李艳华; 周辉云; 王颖; 徐宁迎

    2013-01-01

    microRNA是一种小分子RNA,是细胞内复杂而精确的调控网络的组成部分.为了研究阉割对miR-122和miR-378表达量的影响以及miR-122和miR-378对雄烯酮和粪臭素代谢的调控作用,本研究利用荧光定量PCR检测了miR-122和miR-378在不同生长阶段金华猪(Sus scrofa)公猪肝脏中的表达量变化及其在阉割和非阉割公猪体内表达量的差异,利用高效液相色谱法(high performance liquid chromatography,HPLC)检测了金华猪皮下脂肪的粪臭素含量,并预测了调控pre-miR-122和pre-miR-378转录的相关转录因子及miR-122和miR-378与雄烯酮、粪臭素代谢相关基因的靶关系.结果发现,miR-122在胚胎期高表达,随着日龄的增加表达量逐渐下降;miR-378在胚胎期高表达,生长期呈现先增后减的态势.阉割后两者的表达量均较同期非阉割组表达下调.并且阉割后皮下脂肪中粪臭素的含量显著下降(P<0.01).根据研究结果推测,阉割后激素水平的变化通过相关转录因子影响microRNA的表达,直接或间接影响雄烯酮和粪臭素代谢而实现对公猪膻味性状的调控.而在这个调控网络中,microRNA可能发挥了重要作用,为深入研究公猪膻味性状提供了一个新的思路.%MicroRNA(miRNA) is a class of small RNA,it is involved in the intracellular complicated and precise regulatory networks.In order to study the effect of castration on the expression of miR-122 and miR-378 and the regulation effect of miR-122 and miR-378 on androstenone and skatole metabolism,we detected the skatole content in subcutaneous fat of boars and barrows with the help of high performance liquid chromatography (HPLC) and the expression of miR-122 and miR-378 in various growth stages in liver of Jinhua Pig (Sus scrofa) by quantitative Real-time PCR (qRT-PCR) and analysed the expression variation between boars and barrows.The results showed that the skatole content in adipose tissue was higher (P<0.01) in boars

  4. [Urinary incontinence in castrated bitches. 2. Diagnosis and treatment].

    Science.gov (United States)

    Arnold, S

    1997-01-01

    Urinary incontinence due to spaying is caused by a sphincter incompetence of the urethra. In practice the diagnosis is established by ruling out other causes of incontinence such as neurological disease, bacterial cystitis, urinary tract malformation, iatrogenic ureterovaginal fistula and neoplasia of the urinary tract. An accurate diagnosis of urethral sphincter incompetence is made by urethral pressure profilometry. A urethral closure pressure of 7.4 cm H2O allowed the differentiation of bitches with urinary incontinence, due to spaying, from healthy control dogs with a diagnostic accuracy of 91%. For therapy alpha-adrenergic drugs (Ephedrine or Phenylpropanolamine) are recommended, which result in continence in 74% and improvement in 24% of incontinent patients. In the absence of response estrogens may be used. If the medical therapy fails to achieve urinary continence, the endoscopic injection of collagen into the submucosa of the proximal urethra can be performed. This is a simple and minimally invasive procedure. It rarely leads to complications and may be repeated when necessary. The method is successful in 75% of cases. PMID:9281063

  5. Avaliação do glicogênio hepático correlacionado com glicose sérica em ratas castradas sob tratamento com tibolona Evaluation of hepatic glycogen correlated with serum glucose in castrated rats under tibolone treatment

    Directory of Open Access Journals (Sweden)

    Porphirio José Soares Filho

    2011-10-01

    Full Text Available INTRODUÇÃO: O glicogênio representa a forma de armazenamento de açúcares na célula animal, sendo estocada naturalmente no hepatócito. Em sua dinâmica metabólica ocorre participação de receptores, hormônios e enzimas que mantêm e equilibram os níveis séricos desse componente. OBJETIVO: O presente estudo investigou a influência da tibolona no metabolismo glicídico hepático por meio de avaliação da presença do glicogênio hepático e níveis séricos de glicose. MATERIAL E MÉTODOS: Utilizamos ao todo 14 ratas Wistar, em menopausa cirúrgica comprovada citologicamente, tratadas diariamente com tibolona (n = 9 ou com placebo (n = 5 durante 20 semanas. Efetuou-se avaliação dos pesos do animal e do fígado e dos níveis de glicose sérica. O estudo morfológico foi realizado em cortes histológicos de tecido hepático, corados com hematoxilina e eosina (HE e com ácido periódico de Schiff (PAS, com e sem amilase salivar. Para avaliação do glicogênio no fígado, utilizou-se grade de estudo morfológico (GEM, que delineia as regiões metabólicas e circulatórias do lóbulo hepático. RESULTADOS: O peso dos animais foi menor no Grupo Tibolona, com glicose sérica em níveis mais baixos; já o peso relativo do fígado foi significativamente maior (p INTRODUCTION: Glycogen serves as glucose storage in animals and it is naturally found in hepatocytes. Receptors, hormones and enzymes, which maintain and balance serum levels of this component, participate in its metabolic dynamics. OBJECTIVE: This study investigated the influence of tibolone on the hepatic glycemic metabolism by assessing the presence of liver glycogen and serum glucose. MATERIAL AND METHODS: Fourteen castrated Wistar rats, cytologically validated as surgical menopause models, were treated with tibolone (n = 9 or placebo (n = 5 for 20 weeks. Their body and liver weight and serum glucose levels were assessed. The morphologic study was performed in histological

  6. Redução do nível de proteína bruta e suplementação de aminoácidos em rações para suínos machos castrados mantidos em ambiente termoneutro dos 30 aos 60 kg Reduction of crude protein levels of ration with amino acid supplementation to castrated swines maintained in a termoneutral environment from 30 to 60 kg

    Directory of Open Access Journals (Sweden)

    Rony Antonio Ferreira

    2005-04-01

    Full Text Available Este estudo foi conduzido para avaliar a influência da redução do nível de proteína bruta (PB da ração com suplementação de aminoácidos sobre o desempenho de suínos machos castrados (Landrace x Large White mantidos em ambiente termoneutro. Cinqüenta leitões mestiços (peso médio inicial de 30,2 kg foram distribuídos em delineamento experimental inteiramente ao acaso, com cinco tratamentos (17, 16, 15, 14 e 13% PB, cinco repetições e dois animais por unidade experimental. As rações experimentais e a água foram fornecidas à vontade até o final do experimento, quando os animais atingiram o peso médio de 60,2 kg. A temperatura média no interior da sala foi mantida em 22,0ºC e a umidade relativa média em 82,8%, correspondendo a um índice de temperatura de globo e umidade (ITGU de 69,2. A redução do nível de PB da ração influenciou o ganho de peso (GP dos animais; aqueles que consumiram a ração com 17% de PB apresentaram redução significativa no GP em relação aos que receberam as rações com 15 e 14% de PB. O consumo de ração e a conversão alimentar não foram influenciados pelos tratamentos. A redução do nível de PB aumentou as deposições de gordura e de proteína na carcaça e levou à diminuição da excreção de nitrogênio total. O nível de PB da ração para suínos machos dos 30 aos 60 kg mantidos em ambiente termoneutro pode ser reduzido de 17 para 13%, sem influenciar negativamente o desempenho, desde que as rações sejam devidamente suplementadas com aminoácidos essenciais limitantes.An study was conducted to evaluate the influence of reduction of crude protein (CP levels and amino acid supplementation in diets on the performance of castrated swines (Landracex Large White maintained in a termoneutral environment. Fifty crossbreed piglets (average initial body weight of 30.2 kg were allotted to a completely randomized experimental design with five treatments (17, 16, 15, 14 and 13% CP and

  7. Qualidade e composição química da carne de bovinos de corte inteiros ou castrados de diferentes grupos genéticos Charolês x Nelore Quality and composition of meat from entire or castrated beef cattle from different Charolais x Nellore genetic groups

    Directory of Open Access Journals (Sweden)

    Fabiano Nunes Vaz

    2001-04-01

    Full Text Available Utilizaram-se 70 bovinos machos de três sistemas de acasalamento, puros Charolês (Ch e Nelore (Ne, mestiços G1: 1/2 Ch + 1/2 Ne (1/2 Ch e 1/2 Ne + 1/2 Ch (1/2 Ne e mestiços G2: 3/4 Ch + 1/4 Ne (3/4 Ch e 3/4 Ne + 1/4 Ch (3/4 Ne. O número de animais por grupo genético foi, respectivamente, 15, 12, 8, 12, 14 e 9. Trinta e cinco animais foram castrados (C aos sete meses e 35 foram mantidos inteiros (I. Os animais foram confinados dos 20 aos 24 meses, quando foram abatidos. Para avaliação da carne, foi utilizado o músculo longissimus dorsi. Não houve interação significativa entre grupo genético e estado sexual para nenhuma das variáveis estudadas. Os machos I apresentaram carne mais escura (3,05 contra 3,78 pontos com menor marmoreio (4,26 contra 5,75 pontos e menos extrato etéreo (1,73 contra 2,88%. Entretanto, a área de longissimus dorsi foi maior (66,03 contra 60,50 cm² e a carne com melhor palatabilidade, suculência e mais macia. Na comparação entre grupos genéticos, os Ch apresentaram maior longissimus dorsi. Na primeira geração de cruzamento (G1, animais 1/2 Ch apresentaram maior marmoreio e teor de extrato etéreo e menor quebra à cocção que os 1/2 Ne. Entre os animais G2, os animais 3/4 Ne mostraram maior quebra ao descongelamento e teor de extrato etéreo na carne. Na G1, o nível de heterose chegou a 18,54% para área de longissimus dorsi, 28,10% para teor de extrato etéreo e 64,01% para marmoreio da carne. Na G2, a heterose foi de -17,37% para a textura da carne e 10,40% para área de longissimus dorsi.Seventy beef males of three breeding systems (BS, straightbreds Charolais (Ch and Nellore (Ne, G1 crossbreds: 1/2 Ch + 1/2 Ne (1/2 Ch and 1/2 Ne + 1/2 Ch (1/2 Ne and G2 crossbreds: 3/4 Ch + 1/4 Ne (3/4 Ch and 3/4 Ne + 1/4 Ch (3/4 Ne were used. The number of animals by genetic group was, respectively, 15, 12, 8, 12, 14 and 9. Thirty-five males were castrated (C at seven months and 35 were kept intact (I. The animals

  8. Root of Slave after Ravaging and " Castrating or Spay " by Rural Power --The Second Part of the Series of Research Papers on Theme of "National Character in Novels of Lu Xun and Writers after the 1990s%被乡村权力蹂躏和“阉割”后的奴隶根性——鲁迅与1990年代后中国小说中“国民性”主题系列研究论文(二)

    Institute of Scientific and Technical Information of China (English)

    古大勇

    2012-01-01

    鲁迅小说开创的"国民性"主题在1990年代后中国小说中得到鲜明的承续,例如两者都典型地表现了被乡村权力蹂躏和"阉割"后顽固存留于乡民身上的奴隶根性。此种主题在1990年代后中国小说中频繁再现,表明了"改造国民性"的艰难,20世纪初鲁迅所孜孜以求的"改造国民性"的民族重任并没有完成。%The theme of "national character" created by Lu Xun distinctly continued in novels after the 1990s, for example, both typically displayed the theme of the root of obstinate slave that retained on the villager after ravaging and " castrating or spay " by rural power. This theme appeared frequently in the novels after the 1990s that demonstrated the difficult of transformation of national character.. The task of transformation of national character that proposed by Lu Xun has not completed now yet.

  9. PREVENTION OF COMPLICATIONS IN CASTRATE-REFRACTORY PROSTATE CANCER PATIENTS WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    K. M. Nushko

    2015-01-01

    Full Text Available Abstract:Prostate cancer (PC is one of the most urgent problems in modern oncourology. Every year the world is recording more than 900 thousands new cases of prostate cancer. For this reason, the diagnosis and treatment of this disease has recently been given more attention, both abroad and in the Russian Federation. Despite improvements in diagnostic methods and implementation of programs for active detection of the disease in its early stages, the number of patients suffering from advanced forms of prostate cancer remains high. Currently, the main method of treatment in patients with metastatic prostate cancer remains the hormone therapy (HT. Patients with metastatic prostate cancer most frequently have localization of metastatic lesions in the lymph nodes and bones. Frequent localization of metastatic lesions in the bones is due to tumor cell tropism of prostate cancer to the bone. Metastatic bone disease, as well as long-term HT conducted in patients with metastatic prostate cancer, leads to irreversible disruption of bone remodeling, which may be accompanied by osteoporosis and fragility fractures. Bone metastases in patients with PC are the most common cause of complications and significantly impair the quality of life of patients. Therapy underlying the prevention of bone complications can be specific, aimed directly at the tumor tissue and non-specific, to strengthen bones and decrease its resorption processes. The article provides an overview of the literature covering the effectiveness of modern drugs, aimed at non-specific prevention of bone complications in patients with metastatic prostate cancer, such as bisphosphonates, and inhibitors of the ligand RANKL, as well as an overview of studies to assess the effectiveness of domestic analogue zolendronovoy acid preparation Resorba in the prevention of osteoporosis.

  10. The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, C J; Blake, G M; Iversen, P;

    2003-01-01

    females). Total hip Z-scores were lumbar spine BMD was affected by degenerative disease. These preliminary data suggest that there may be an advantage in terms of BMD in using bicalutamide monotherapy compared...

  11. Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone

    DEFF Research Database (Denmark)

    Brasso, Klaus; Thomsen, Frederik B; Schrader, Andres J;

    2015-01-01

    prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. RESULTS AND LIMITATIONS: We identified 137 patients who prior to enzalutamide had progressed following a median....... Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS. CONCLUSIONS: Median OS...

  12. Alarin stimulates food intake in male rats and LH secretion in castrated male rats

    OpenAIRE

    Van Der Kolk, Nicole; Madison, Farrah N.; Mohr, Margaret; Eberhard, Nicole; Kofler, Barbara; Fraley, Gregory S.

    2010-01-01

    Alarin is a newly identified member of the galanin family of neuropeptides that includes galanin-like peptide (GALP) and galanin. Alarin was discovered as an alternate transcript of the GALP gene in neuroblastoma cells, and subsequently alarin mRNA was detected in the brain of rodents. GALP and galanin are important central regulators of both feeding and reproductive behavior. We hypothesized, that, as a member of the galanin family of peptides, alarin would also have central effects on feedi...

  13. PREVENTION OF COMPLICATIONS IN CASTRATE-REFRACTORY PROSTATE CANCER PATIENTS WITH BONE METASTASES

    OpenAIRE

    K. M. Nushko; A. S. Kalpinskiy; A. D. Kaprin

    2015-01-01

    Abstract:Prostate cancer (PC) is one of the most urgent problems in modern oncourology. Every year the world is recording more than 900 thousands new cases of prostate cancer. For this reason, the diagnosis and treatment of this disease has recently been given more attention, both abroad and in the Russian Federation. Despite improvements in diagnostic methods and implementation of programs for active detection of the disease in its early stages, the number of patients suffering from advanced...

  14. Clinical and Preclinical Treatment Aspects of Castration Resistant Prostate Cancer (CRPC)

    NARCIS (Netherlands)

    H.J. Meulenbeld (Hielke)

    2012-01-01

    textabstractIn the Western countries prostate cancer is the most frequently diagnosed cancer, except for skin cancer, and the second leading cause of male cancer deaths. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men,

  15. [Medical castration in the treatment of locally advanced or metastatic prostate cancer: an update].

    Science.gov (United States)

    Drouin, S-J; Rouprêt, M; Davin, J-L; Soulié, M

    2009-04-01

    Indications for hormonotherapy in prostate cancer are in deep mutation and are constantly evolving. Used initially (1941) in metastatic stages, hormone therapy is used nowadays in locally advanced prostate cancer and aggressive localized disease. Its prescription in association with radiotherapy or surgery has provided a benefit regarding survival free progression. The place of hormone therapy in localized prostate cancer is not well defined and the debate is still ongoing, especially in case of biochemical recurrence after irradiation or radical prostatectomy and even in neoadjuvant cases. Additional and further studies are ongoing and are strongly needed to establish new guidelines. Nevertheless, hormone therapy is not restricted any more to palliative cases and is part of the current therapeutic arsenal of the urologist for high risk localized and/or locally advanced prostate cancers. PMID:19465332

  16. Effects of castration and time-on-feed on Mertolenga breed beef quality.

    Science.gov (United States)

    Monteiro, A C G; Navas, D R; Lemos, J P C

    2014-04-01

    Physicochemical characteristics were determined in the longissimus lumborum muscle, after 8 days of ageing of steers (n=12) and bulls (n=12) from Mertolenga breed slaughtered directly from pasture (day 0) or after a finishing period of 50, 100 and 150 days in a feed-lot facility. Bulls and steers presented similar live weight (averaging 388 kg), carcass weight (CW; averaging 213 kg), dressing percentage (averaging 60%), carcass fatness (11.9% CW) and carcass fat thickness (averaging 3.03 mm). Live weight, CW, carcass fatness and fat thickness increased along time-on-feed. Gender only had a negligible effect on meat characteristics, with b and h being the only parameters of colour affected by gender, also presenting a significant interaction gender × time-on-feed. Nevertheless, both the genders presented a high-quality grade concerning tenderness (Warner-Bratzler shear force (WBSF)). L increased until 50 days on feed and decreased afterwards, whereas a and C values increased along time-on-feed. Pigment content was also affected by time-on-feed and showed a gender × time-on-feed interaction. Beef colour became darker and redder along time-on-feed, but still in a colour range highly acceptable by Portuguese consumers. Despite the increase in intramuscular fat and myofibrillar fragmentation index, as well as the decrease in collagen content of steers and bulls along time-on-feed, it did not affect the tenderness/hardness, indicating a small effect of time-on-feed in meat characteristics. Despite only small differences in carcass characteristics and meat-quality parameters that have been noticed along time-on-feed, those differences were only significant after 100 days on feed. Principal component analysis (PCA) was performed. The first PC axis (39.6% of the total variance) included colour variables a, b and C, and carcass fatness, fat thickness, CW and live weight, whereas the second one (12.7% of the total variance) included h, cooking losses and dressing-out. The principal component (PC) analysis confirmed the lack of differences between bulls and steers and indicates a differentiation of the first two periods of feeding (0 and 50 days on feed) from the two latter (100 and 150 days on feed) periods of feeding. PMID:24636828

  17. [Urinary incontinence in castrated bitches. Part 1: Significance, clinical aspects and etiopathogenesis].

    Science.gov (United States)

    Arnold, S

    1997-01-01

    Acquired urinary incontinence occurs in 20% of spayed dogs and there exists a strong correlation between body weight and the risk of urinary incontinence. Bitches with a body weight of more than 20 kg have a risk of 30% white smaller dogs have a risk of 10%. A particular breed disposition exists in Boxers in which 65% are affected. Other breeds with a more than average disposition for urinary incontinence are Dobermans and Giant Schnauzers. Urinary incontinence due to spaying manifests itself mainly while the dogs are sleeping. The cause is a urethral sphincter incompetence which can be verified by a urethral pressure profile (UPP). The microtransducer method proved to be a suitable method for urodynamic studies. It could be demonstrated that the urethral closure pressure is significantly lower in incontinent bitches (4.6 +/- 2.3 cm H2O) than in continent bitches (18.6 +/- 10.5 cm H2O). In addition, the urethral closure pressure for continent bitches dropped significantly within 12 months after surgery. Histological examination revealed that the functional urethral closure cannot be explained by the extent of discernible structures of the urethral wall as seen by light microscopy. PMID:9411733

  18. Tissue culture media supplemented with 10% fetal calf serum contains a castrate level of testosterone.

    NARCIS (Netherlands)

    Sedelaar, J.P.M.; Isaacs, J.T.

    2009-01-01

    BACKGROUND: Human prostate cancer cells are routinely maintained in media supplemented with 10% Fetal Calf Serum (FCS) to provide androgen. In the present study, total and free testosterone levels in 10%FCS supplemented tissue culture media were determined and compared to levels in intact and castra

  19. Radium-223 treatment of bone metastases from castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Mortensen, Jann; Højgaard, Liselotte

    2014-01-01

    The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline...... phosphatase- and PSA level and prolonged survival. Adverse events are usually mild to moderate and comprise gastrointestinal and myelotoxic symp-toms. Intravenously administered (22)3Ra-Cl2 (half-life 11.4 days) will likely be given every four weeks for six treatments to out-patients....

  20. BAY 1024767 blocks androgen receptor mutants found in castration-resistant prostate cancer patients.

    Science.gov (United States)

    Sugawara, Tatsuo; Lejeune, Pascale; Köhr, Silke; Neuhaus, Roland; Faus, Hortensia; Gelato, Kathy A; Busemann, Matthias; Cleve, Arwed; Lücking, Ulrich; von Nussbaum, Franz; Brands, Michael; Mumberg, Dominik; Jung, Klaus; Stephan, Carsten; Haendler, Bernard

    2016-02-01

    Androgen receptor (AR) mutations arise in patients developing resistance to hormone deprivation therapies. Here we describe BAY 1024767, a thiohydantoin derivative with strong antagonistic activity against nine AR variants with mutations located in the AR ligand-binding domain (LBD), and against wild-type AR. Antagonism was maintained, though reduced, at increased androgen levels. Anti-tumor efficacy was evidenced in vivo in the KuCaP-1 prostate cancer model which bears the W741C bicalutamide resistance mutation and in the syngeneic prostate cancer rat model Dunning R3327-G. The prevalence of six selected AR mutations was determined in plasma DNA originating from 100 resistant patients and found to be at least 12%. Altogether the results show BAY 1024767 to be a strong antagonist for several AR mutants linked to therapy resistance, which opens the door for next-generation compounds that can benefit patients based on their mutation profile.

  1. Control of the misuse of testosterone in castrated horses based on an international threshold in plasma.

    Science.gov (United States)

    Ho, Emmie N M; Kwok, W H; Leung, David K K; Riggs, Christopher M; Sidlow, Gordon; Stewart, Brian D; Wong, April S Y; Wan, Terence S M

    2015-05-01

    Testosterone is an endogenous steroid produced primarily in the testes. Trace levels of testosterone are found in urine samples from geldings, as testosterone is also secreted by the adrenal. An international threshold of free and conjugated testosterone in urine (20 ng/mL) was adopted by the International Federation of Horseracing Authorities (IFHA) in 1996 for controlling testosterone misuse in geldings. In view of the recent popularity of using blood in doping control testing, it is necessary to establish a threshold for testosterone in gelding plasma. A liquid chromatography-mass spectrometry (LC/MS) method was developed for quantifying low levels of free testosterone in gelding plasma. Based on a population study of 152 post-race plasma samples, the mean ± SD concentration of plasma testosterone was determined to be 14.7 ± 6.8 pg/mL. Normal distribution could be obtained after square-root or cube-root transformation, resulting in respective tentative thresholds of 49 or 55 pg/mL (corresponding to a risk factor of less than 1 in 10 000). A rounded-up threshold of 100 pg/mL of free testosterone in plasma was proposed. Based on the administration of Testosterone Suspension 100 to six geldings, the same average detection time of 14 days was observed in either plasma or urine using the proposed plasma threshold and the existing international urine threshold. The maximum detection time was 18 days in plasma and 20 days in urine. The results demonstrated the proposed plasma threshold is effective in controlling the misuse of testosterone in geldings. Similar results were subsequently obtained in Europe, and this proposed threshold was adopted by IFHA in October 2013. PMID:24889217

  2. Return to fertility after extended chemical castration with a GnRH antagonist

    International Nuclear Information System (INIS)

    Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist

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

    Science.gov (United States)

    2014-11-21

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

  4. Administration of perioperative penicillin reduces postoperative serum amyloid A response in horses being castrated standing

    DEFF Research Database (Denmark)

    Busk, Peter; Jacobsen, Stine; Martinussen, Torben

    2010-01-01

    Objectives: To compare postoperative inflammatory responses in horses administered perioperative procaine penicillin and those not administered penicillin using acute phase protein serum amyloid A (SAA) as a marker of inflammation. Study Design: Randomized clinical trial. Animals: Stallions (n = 50...... administered NSAID and 25,000 U/kg procaine penicillin on day 0, 1, and 2. Results: SAA concentrations increased significantly from preoperative levels in both groups, and on day 8 concentrations were significantly (P o .02) higher in horses administered only NSAID than in those administered procaine penicillin...

  5. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer1

    OpenAIRE

    Brown, Janet E.; Sim, Sheryl

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  6. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer

    OpenAIRE

    Brown, Janet E.; Sheryl Sim

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  7. Metabolism of adrenal androgen and its impacts on prostate cancer after castration

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ With the extensive utilization of PSA,digital rectum examination and transrectal ultrasound for screening in the aging population,the diagnosis of prostate cancer in China has markedly increased during the past years,particularly in developed regions.

  8. The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, C J; Blake, G M; Iversen, P;

    2003-01-01

    females). Total hip Z-scores were spine BMD was affected by degenerative disease. These preliminary data suggest that there may be an advantage in terms of BMD in using bicalutamide monotherapy compared...

  9. Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

    OpenAIRE

    Rennie, Paul S.; Artem Cherkasov; Nada Lallous; Kush Dalal

    2013-01-01

    Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR) is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the ...

  10. "I Hope Someone Castrates You, You Perverted Bastard": Martin Cole's Sex Education Film, "Growing Up"

    Science.gov (United States)

    Limond, David

    2009-01-01

    This paper concerns the response to the sex education film "Growing Up", made in 1971 by Dr Martin Cole, which used a combination of animation and live action to offer a frank and uncompromising account of sexual reproduction. As part of this, both male and female masturbation and an unsimulated act of male-female coitus featured in the film. Cole…

  11. Increased expression of class III β-tubulin in castration-resistant human prostate cancer

    OpenAIRE

    Terry, S; Ploussard, G; Allory, Y; Nicolaiew, N; Boissière-Michot, F; Maillé, P; Kheuang, L; Coppolani, E; Ali, A.; Bibeau, F; Culine, S; Buttyan, R.; de la Taille, A; Vacherot, F

    2009-01-01

    Background: Class III β-tubulin (βIII-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of βIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, βIII-tubulin expression remains largely uncharacterised in prostate cancer. Methods: In this report, we evaluated the expression of βIII-tubulin in 138 d...

  12. New therapies for relapsed castration-resistant prostate cancer based on peptide analogs of hypothalamic hormones

    Directory of Open Access Journals (Sweden)

    Andrew V Schally

    2015-01-01

    Full Text Available It is a pleasure to contribute our presentation at the International Prostate Forum of the Annual Meeting of the American Urological Association (AUA to this special issue of the Asian Journal of Andrology.

  13. Parasitic castration in Fissurella crassa (Archaeogastropoda due to an adult Digenea, Proctoeces lintoni (Fellodistomidae

    Directory of Open Access Journals (Sweden)

    Marcelo E. Oliva

    1992-03-01

    Full Text Available Specimens of Fissurella crassa (Archaeogastropoda from Ilo, southern Perú, are infected with the adult stage of the digenetic trematode Proctoeces lintoni (Fellodistomidae. The histopatological analysis of the male and female gonads show a strong effect of the parasite on the structure and function of these organs. P. lintoni live unencysted in the gonads, and the main mechanical damage is originated by the action of a well developed acetabulum. Chemical actions of parasitic secretions may also be involved. The infected gonads show altered structure and the gametogenic processes is aborted. There is no evidence of hemocytic response, but leucocite infiltration is evident at least in male infected gonads. An increased content of polysaccarides is evident in infected gonads.

  14. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana;

    2016-01-01

    progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; pdeath by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm...... the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic....... Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue...

  15. The Hippo Pathway Effector YAP Regulates Motility, Invasion, and Castration-Resistant Growth of Prostate Cancer Cells

    OpenAIRE

    Lin ZHANG; Yang, Shuping; Chen, Xingcheng; Stauffer, Seth; Yu, Fang; Lele, Subodh M.; Fu, Kai; Datta, Kaustubh; Palermo, Nicholas; Chen, Yuanhong; Dong, Jixin

    2015-01-01

    Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway. The functional significance of YAP in prostate cancer has remained elusive. In this study, we first show that enhanced expression of YAP is able to transform immortalized prostate epithelial cells and promote migration and invasion in both immortalized and cancerous prostate cells. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2 cells) compared to t...

  16. Diving Into Cabazitaxel's Mode of Action: More Than a Taxane for the Treatment of Castration-Resistant Prostate Cancer Patients.

    Science.gov (United States)

    Mellado, Begoña; Jimenez, Natalia; Marin-Aguilera, Mercedes; Reig, Oscar

    2016-08-01

    Prostate cancer is a molecularly heterogeneous disease, and mechanisms of action of taxanes and potential mechanisms of resistance are not clearly defined. Taxanes are microtubule-stabilizing agents resulting in the slowing or blocking of mitosis at the metaphase-anaphase transition and induction of apoptotic cell death. Taxanes also can inhibit androgen receptor pathway. To date, several factors have been associated with taxane resistance, including alterations in tubulin, the effect of drug efflux pumps, and the dysfunctional regulation of signaling pathways that may be involved in resistance to therapy. Preclinical and clinical data support the distinct activity of cabazitaxel in prostate cancer that may overcome resistance to prior taxanes or hormonal therapies. It is challenging to define the most adequate therapeutic sequence for each patient. Moreover, the identification of molecular markers of resistance may help to select patients for specific therapies. PMID:26827258

  17. Multiplexed Quantum Dot Labeling of Activated c-Met Signaling in Castration-Resistant Human Prostate Cancer

    OpenAIRE

    Peizhen Hu; Gina C-Y Chu; Guodong Zhu; Hua Yang; Daniel Luthringer; Gail Prins; Fouad Habib; Yuzhuo Wang; Ruoxiang Wang; Chung, Leland W. K.; Zhau, Haiyen E.

    2011-01-01

    The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularl...

  18. Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette;

    2015-01-01

    incidence of peripheral edema (32% vs. 15%, Pfebrile neutropenia in this group (25% vs. 10%, P...% CI: 0.76-1.26, P = 0.89, Cox proportional hazard regression model). CONCLUSIONS: Coadministration of low-dose P reduced the incidence of peripheral edema, grade 3 nonhematological toxicity, and the risk of being admitted owing to febrile neutropenia during treatment with D. Adjusted survival analysis...

  19. LHRH agonists in prostate cancer : frequency of treatment, serum testosterone measurement and castrate level: consensus opinion from a roundtable discussion

    NARCIS (Netherlands)

    de Jong, Igle Jan; Eaton, Alan; Bladou, Franck

    2007-01-01

    Background: Options for lowering testosterone in patients with prostate cancer include bilateral orchiectomy, oestrogens and luteinising hormone-releasing hormone (LHRH) agonists. LHRH agonists have become widely used in the treatment of prostate cancer. Roundtable assembly: In May 2006, a team of e

  20. RECEITA INDUSTRIAL DE CORTES SECUNDÁRIOS DA CARCAÇA DE BOVINOS MESTIÇOS LEITEIROS, NÃO CASTRADOS OU SUBMETIDOS A DIFERENTES FORMAS DE CASTRAÇÃO

    OpenAIRE

    Fabiano Nunes Vaz; João Restle; João Teodoro Pádua; Danielle Curado de Santana Morale; Paulo Santana Pacheco; Cristiano Sales Prado

    2015-01-01

    The objective of this study was to assess the income and revenues from the sale of boneless cuts of the carcass of 84 Holstein x Zebu crossbred males, non-castrated or submitted to different castration methods at twelve month of age. The animals were randomly divided into four treatments with 21 replications each: castrated with burdizzo, castrated by removing the scrotum apex, castrated with lateral incisions in the scrotum and non-castrated. The slaughter of animals occurred on the sa...

  1. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Graff, J N; Baciarello, G; Armstrong, A J;

    2016-01-01

    -resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged ... for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited from treatment with enzalutamide...... in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged falls. CLINICAL TRIAL IDENTIFIER: NCT01212991, ClinicalTrials.gov....

  2. Improved outcomes in elderly patients with metastatic castration-resistant prostate cancer treated with the androgen receptor inhibitor enzalutamide: results from the phase III AFFIRM trial

    NARCIS (Netherlands)

    Sternberg, C.N.; Bono, J.S. de; Chi, K.N.; Fizazi, K.; Mulders, P.; Cerbone, L.; Hirmand, M.; Forer, D.; Scher, H.I.

    2014-01-01

    BACKGROUND: The randomized, double-blind phase III AFFIRM trial demonstrated that enzalutamide, an oral androgen receptor inhibitor, significantly prolonged overall survival (OS) [median 18.4 versus 13.6 months (hazard ratio, HR) 0.63 (95% confidence interval, CI, 0.53-0.75); P<0.001] compared wi

  3. Treatment of Bone Metastases with Radium-223 in Patients with Castration Resistant Prostate Cancer (CRPC): Alternative or Complementary to Innovative Molecular Therapies?

    International Nuclear Information System (INIS)

    The skeletal metastatic disease is a real clinical problem. Approximately 70% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will develop skeletal metastases, which cause considerable morbidity. Several options are available for treatment, to be used either alone or in various combinations: hormones in case of hormone-sensitive tumours, chemotherapy, biphosphonates, external beam radiation therapy, surgery (in pathologic or impending fracture), bone-seeking radiopharmceuticals, and also molecular therapies. Focusing our attention to patients with prostate cancer, 50% of patients with bone metastases develop skeletal related events (SREs) such as: severe pain, pathologic fractures, spinal compression syndrome, malignant hypercalcemia, bone marrow suppression. All these SREs require adequate therapy since generally determine several functional impairments and worsen the prognosis. It is well known that skeletal complications reduce the quality of life affecting different aspects, physical, functional end emotional. SREs are associated also with lower survival

  4. 68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer.

    Science.gov (United States)

    Ahmadzadehfar, Hojjat; Schlenkhoff, Carl Diedrich; Rogenhofer, Sebastian; Yordanova, Anna; Essler, Markus

    2016-09-01

    A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases. PMID:27405025

  5. Matrine inhibits the proliferation, invasion and migration of castration-resistant prostate cancer cells through regulation of the NF-κB signaling pathway.

    Science.gov (United States)

    Li, Qi; Lai, Yiming; Wang, Chengbin; Xu, Guibin; He, Zheng; Shang, Xiaohong; Sun, Yi; Zhang, Fan; Liu, Leyuan; Huang, Hai

    2016-01-01

    Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. It has been demonstrated to exhibit antiproliferative properties, promote apoptosis and inhibit cell invasion in a number of cancer cell lines. It has also been shown to improve the efficacy of chemotherapy when it is combined with other chemotherapy drugs. However, the therapeutic efficacy of matrine for prostate cancer remains poorly understood. In the present study, we showed that matrine inhibited the proliferation, migration and invasion of both DU145 and PC-3 cells in a dose- and time-dependent manner. It also reduced the cell population at S phase and increased the cell population at sub-G1 phase. The increases in both the apoptotic cell population and cell population at S and sub-G1 phases consistently indicated a pro-apoptotic effect of matrine. Decreases in levels of P65, p-P65, IKKα/β, p-IKKα/β, IKBα and p-IKBα as detected by immunoblot analysis in the matrine-treated DU145 and PC-3 cells suggested an involvement of the NF-κB signaling pathway. Therefore, it is a novel promising addition to the current arsenal of chemotherapy drugs for the treatment of androgen-independent prostate cancer.

  6. Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Kalevi Kairemo

    2015-07-01

    Full Text Available Radium-223-dichloride (223RaCl2 is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of 223RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (<1.1% gamma radiation at 0, 7 and 28 days using 30–60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1, and from 37.4 to 82.2 (patient 2. The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1, and from 1.5 days to 3.6 days (patient 2, respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6. Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6. Our recommendation based on statistical simulation analysis, is serial measurement at days 0–8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had originally two metastatic sites in the imaging field; the former patient demonstrated a serum PSA response and the latter demonstrated no PSA response. In these two patients there was no significant difference in the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the quantitative imaging. Our results, although preliminary, suggest that dose monitoring can be included as a part of this treatment modality. On the other hand, from the absorbed radiation doses, the response cannot be predicted because with very similar doses, only the former patient responded.

  7. The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration.

    Science.gov (United States)

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lobato, Carlos; Pina, Francisco; Maurício, Joaquina; Monteiro, Cátia; Sousa, Hugo; Calais da Silva, F; Lopes, Carlos; Medeiros, Rui

    2014-01-01

    The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.

  8. Weekly low-dose docetaxel is an effective treatment with fewer adverse events for metastatic castration-resistant prostate cancer in Taiwanese patients

    Directory of Open Access Journals (Sweden)

    Cheng-Li Kao

    2015-12-01

    Conclusion: For Taiwanese mCRPC patients, weekly DTX 30 mg/m2 is an efficient regimen for disease control with relatively low Grade 3 or 4 hematological adverse effects. The proper treatment duration of DTX therapy for mCRPC in Taiwanese patients is still uncertain, so further research is needed.

  9. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Tyrrell, C J; Kaisary, A V; Iversen, P;

    1998-01-01

    To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer.......To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer....

  10. GnRH-A主动免疫家兔的去势效果%Castration by GnRH-A Active Immunization in Rabbits

    Institute of Scientific and Technical Information of China (English)

    魏锁成; 张剑

    2009-01-01

    为了探讨促性腺激素释放激素类似物(gonadotropin releasing hormone analogue,GnRH-A)对动物免疫去势的效果及作用机理.在30只日本大耳白兔(Oryctolagus cuniculus)(EG-Ⅰ与EG-Ⅱ组)的颈背部皮下分2.3点注射1.0ml(100/gml)自制的GnRH-A抗原乳剂,EG-Ⅱ组3周后加强免疫一次;测定睾丸长度与重量、体重、血清GnRH抗体效价及睾酮浓度.结果表明,EG-Ⅱ组睾丸长度与EG-I组差异极显著(P<0.01);EG-Ⅱ组的GnRH抗体水平明显高于EG-Ⅰ组;EG-Ⅱ组、EG-Ⅰ组与对照组的血清睾酮浓度差异逐渐增加,102 d时EG-Ⅱ组睾酮浓度极显著低于对照组(P<0.01),且第28 d后EG-Ⅱ组睾酮浓度显著低于EG-Ⅰ组(P<0.05);EG-Ⅱ组体重和日增重最大,显著高于EG-Ⅰ组及对照组(P<0.05).GnRH-A主动免疫家兔对睾丸发育、血清GnRH抗体效价和睾酮浓度具有显著的影响,加强免疫效果更理想.

  11. Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer.

    Science.gov (United States)

    Narizhneva, Natalia V; Tararova, Natalia D; Ryabokon, Petro; Shyshynova, Inna; Prokvolit, Anatoly; Komarov, Pavel G; Purmal, Andrei A; Gudkov, Andrei V; Gurova, Katerina V

    2009-12-15

    In prostate cancer (PCa) patients, initial responsiveness to androgen deprivation therapy is frequently followed by relapse due to development of treatment-resistant androgen-independent PCa. This is typically associated with acquisition of mutations in AR that allow activity as a transcription factor in the absence of ligand, indicating that androgen-independent PCa remains dependent on AR function. Our strategy to effectively target AR in androgen-independent PCa involved using a cell-based readout to isolate small molecules that inhibit AR transactivation function through mechanisms other than modulation of ligand binding. A number of the identified inhibitors were toxic to AR-expressing PCa cells regardless of their androgen dependence. Among these, some only suppressed PCa cell growth (ARTIS), while others induced cell death (ARTIK). ARTIK, but not ARTIS, compounds caused disappearance of AR protein from treated cells. siRNA against AR behaved like ARTIK compounds, while a dominant negative AR mutant that prevents AR-mediated transactivation but does not eliminate the protein showed only a growth suppressive effect. These observations reveal a transcription-independent function of AR that is essential for PCa cell viability and, therefore, is an ideal target for anti-PCa treatment. Indeed, several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization.

  12. RM8 – Comparison of Timed Automata with Discrete Event Simulation for Modeling Personalized Treatment Decisions: the Case of Metastatic Castration Resistant Prostate Cancer

    NARCIS (Netherlands)

    Degeling, K.; Koffijberg, H.; Schivo, S.; Langerak, R.; IJzerman, M.J.

    2015-01-01

    Objectives The aim of this study is to compare the usefulness of two promising alternative modeling techniques, Timed Automata (TA) originating from informatics, and Discrete Event Simulation (DES) known in operations research, for modeling todays complex and personalized treatment decisions over ti

  13. Effects of acute and chronic cocaine administration on EEG and behaviour in intact and castrated male and intact and ovariectomized female rats

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Dirksen, R.; Vree, T.B.; Haaren, F. van

    1996-01-01

    Intact and gonadectomized male and female WAG/Rij rats were used to study the effects of gender and gonadal hormones on the development of sensitization and tolerance to cocaine-induced changes in EEG and behaviour. The four groups of WAG/Rij rats differed in the number of spontaneously occurring sp

  14. Removing the taint : bottlenecks and possible directions for a solution in the marketing of the meat of non-castrated male pigs

    NARCIS (Netherlands)

    Klep, L.M.F.

    2008-01-01

    Onderzoeksresultaten laten zien dat het onwaarschijnlijk is dat er een eenvoudige oplossing bestaat voor het stoppen met castratie van beertjes in de varkenshouderij. Er dient gezocht te worden naar een combinatie van verschillende methoden. De berengeurproblematiek is primair een probleem van markt

  15. Matrine inhibits the proliferation, invasion and migration of castration-resistant prostate cancer cells through regulation of the NF-κB signaling pathway.

    Science.gov (United States)

    Li, Qi; Lai, Yiming; Wang, Chengbin; Xu, Guibin; He, Zheng; Shang, Xiaohong; Sun, Yi; Zhang, Fan; Liu, Leyuan; Huang, Hai

    2016-01-01

    Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. It has been demonstrated to exhibit antiproliferative properties, promote apoptosis and inhibit cell invasion in a number of cancer cell lines. It has also been shown to improve the efficacy of chemotherapy when it is combined with other chemotherapy drugs. However, the therapeutic efficacy of matrine for prostate cancer remains poorly understood. In the present study, we showed that matrine inhibited the proliferation, migration and invasion of both DU145 and PC-3 cells in a dose- and time-dependent manner. It also reduced the cell population at S phase and increased the cell population at sub-G1 phase. The increases in both the apoptotic cell population and cell population at S and sub-G1 phases consistently indicated a pro-apoptotic effect of matrine. Decreases in levels of P65, p-P65, IKKα/β, p-IKKα/β, IKBα and p-IKBα as detected by immunoblot analysis in the matrine-treated DU145 and PC-3 cells suggested an involvement of the NF-κB signaling pathway. Therefore, it is a novel promising addition to the current arsenal of chemotherapy drugs for the treatment of androgen-independent prostate cancer. PMID:26497618

  16. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer

    DEFF Research Database (Denmark)

    Idorn, Manja; Køllgaard, Tania; Kongsted, Per;

    2014-01-01

    function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies......Myeloid-derived suppressor cells (MDSC) are believed to play a role in immune suppression and subsequent failure of T cells to mount an efficient anti-tumor response, by employing both direct T-cell inhibition as well as induction of regulatory T cells (Tregs). Investigating the frequency and...... correlated positively with Treg levels. In vitro proliferation assay with autologous T cells confirmed M-MDSC-mediated T-cell suppression, and intracellular staining of immune suppressive enzyme iNOS revealed a higher expression in M-MDSC from patients with PC. Increased frequencies of M-MDSC correlated with...

  17. Lipidic characterization of Santa Inês lamb shoulder

    Directory of Open Access Journals (Sweden)

    Christian Albert Carvalho da Cruz

    2011-06-01

    Full Text Available The edible portion of the shoulder of 12 castrated and 12 non-castrated Santa Inês lambs slaughtered at different ages (84, 168, 210, 252 days were used. The shoulders were chemically analyzed to determine the quantity of total lipids, cholesterol, and fatty acids composition. Castrated and non-castrated lambs gained body weight (p = 0.0393, p = 0.0017 and half carcass weight (p = 0.0240, p = 0.0017, respectively. The shoulder weight was increased in the carcasses of non-castrated lambs (p = 0.0110. The edible portion of the shoulder of castrated lambs presented higher total lipids (16.09 g.100 g-1. The cholesterol content was influenced by castration (p = 0.0001 reducing with age. Castrated animals presented higher content of C18:1 T11, CLA, and C18:0. The shoulder weight is only increased with increasing age in the carcasses of non-castrated lambs. Castration influences the cholesterol content of the shoulder; however, both castrated and non-castrated lambs had their cholesterol contents reduced with increasing age. Castration and age interfered in the estearic acid concentration of the edible portion of lamb shoulder.

  18. Lipidic characterization of Santa Inês lamb shoulder

    OpenAIRE

    Christian Albert Carvalho da Cruz; Cristiane Leal dos Santos-Cruz; Carmen Josefina Contreras Castillo; Alexilda Oliveira de Souza; Lílian Borges da Silva; Priscila Nunes Brito

    2011-01-01

    The edible portion of the shoulder of 12 castrated and 12 non-castrated Santa Inês lambs slaughtered at different ages (84, 168, 210, 252 days) were used. The shoulders were chemically analyzed to determine the quantity of total lipids, cholesterol, and fatty acids composition. Castrated and non-castrated lambs gained body weight (p = 0.0393, p = 0.0017) and half carcass weight (p = 0.0240, p = 0.0017), respectively. The shoulder weight was increased in the carcasses of non-castrated lambs (p...

  19. Criminología Mediática, castración química a violadores y política criminal: ¿Eficientismo antigarantista?/Mediatic criminology, chemical castration to rappers and criminal policy

    Directory of Open Access Journals (Sweden)

    Italy Ciani Sotomayor

    2013-01-01

    Full Text Available La inseguridad que vivimos hoy en día y el hecho de que la mayoría de los delitos cometidos queden impunes ante la ineficacia de la gran mayoría de instituciones dedicadas a la procuración e impartición de justicia, han maximizado el fenómeno criminal. Los políticos, como una manera de reaccionar ante ello, es frecuente que pugnen por la creación de más delitos y penas más severas, creyendo que con esto mandan un mensaje positivo a la sociedad: tanto a víctimas como a criminales. Analizaremos el caso específico de la castración química como solución para frenar el delito de violación. Lo cierto es que estas propuestas casi siempre resultan contraproducentes, no nos hacen sentir más seguros y mucho menos inhiben la comisión de delitos, pues no es la forma de prevenirlos. El problema de fondo, como veremos, se encuentra en la ineficiencia del sistema de justicia penal mexicano, en la equivocada política criminal que hemos adoptado y en la ausencia de una política criminológica.

  20. 重读红色:浩然小说主人公眼里的阉割与乱伦%Red Reread: Castration and Incest for the People in Hao Ran's Stories

    Institute of Scientific and Technical Information of China (English)

    田晓菲

    2010-01-01

    @@ 文学作品总要放到上下文里来读.语境对于意义生产至关重要,也能让作品中未曾被发现的内容浮出水面.对社会主义中国"红色经典"的故事新编向我们揭示出原作情节与人物塑造本身潜在的意义或可能性.本篇论文以浩然(1932-2008)的两个短篇小说为例,说明将红色经典置于一个不同语境下进行重读也能产生同样效果.浩然也许是文化大革命时期最受欢迎的作家.他的长篇小说堪称"中国特色社会主义"真正的史诗,销量已经过百万;他的短篇小说在批评界受到的关注虽然不及长篇,却充分表现了阅读模式的变化如何影响文本的意义.然而,变化的阅读模式并不总是"事后"发生.

  1. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

    NARCIS (Netherlands)

    Eertwegh, A.J. van den; Versluis, J.; Berg, H.P. van den; Santegoets, S.J.; Moorselaar, R.J. van; Sluis, T.M. van der; Gall, H.E.; Harding, T.C.; Jooss, K.; Lowy, I.; Pinedo, H.M.; Scheper, R.J.; Stam, A.G.; Blomberg, B.M. von; Gruijl, T.D. de; Hege, K.; Sacks, N.; Gerritsen, W.R.

    2012-01-01

    BACKGROUND: The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte ant

  2. 蛇床子素对去势大鼠雄激素水平和-氧化氮合酶的影响%Effects of Osthol on Androgen Level and Nitric Oxide Synthase Activity in Castrate Rats

    Institute of Scientific and Technical Information of China (English)

    袁娟丽; 谢金鲜; 李爱媛; 周芳

    2004-01-01

    目的:研究蛇床子素对雄性激素水平及一氧化氮合酶活性的影响.方法:采用幼年去势雄性大鼠连续灌胃蛇床子素20天后,测定大鼠血清睾酮(T)、黄体生成素(LH)、卵泡刺激素(FSH)含量,测定阴茎组织中一氧化氮合酶(NOS)活性、一氧化氮(NO)含量.结果:蛇床子素高剂量组可升高T、LH、FSH含量(P《0.05或P《0.01).蛇床子素高、低剂量均可显著增加NOS含量(P《0.01).结论:蛇床子素可提高去势大鼠雄激素、促性腺激素含量及一氧化氮合酶的活性,提示蛇床子素具有雄激素样作用和促性腺激素样作用.

  3. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory. (orig.)

  4. Morfologia e histoquímica da pele de ratas hipotireóideas castradas e não castradas Morfology and histochemistry of the skin in hypothyroid castrated and intact rats

    OpenAIRE

    E. Ferreira; R. Serakides; V.A. Nunes; M.G. Gomes; C.M. Silva; N.M. Ocarino; A.F.C. Ribeiro

    2003-01-01

    Foram estudadas as alterações cutâneas de ratas Wistar adultas castradas e não castradas, mantidas em estado hipotireóideo por 120 dias. Dois grupos eutireóideos, um castrado e outro não castrado, serviram de controle. Secções da pele abdominal ventral e torácica dorsal foram coradas pelas técnicas de HE, PAS, azul de alcian (alcian blue), picro-sirius red-luz polarizada e Verhoeff. Adelgaçamento da epiderme, atrofia de glândulas sebáceas, redução parcial ou total de fibras elásticas e do col...

  5. CARACTERÍSTICAS DE CARCAÇA E DA CARNE DE BOVINOS MESTIÇOS NÃO-CASTRADOS OU SUBMETIDOS A DIFERENTES MÉTODOS DE CASTRAÇÃO

    Directory of Open Access Journals (Sweden)

    Fabiano Nunes Vaz

    2014-12-01

    Full Text Available The objective of this study was to assess the effects of different castration methods applied to dairy crossbred males on carcass and meat traits, compared with noncastrated animals. Eighty-four males, with average age of ten months, were randomized into four groups of 21 animals: castrated using burdizzo tool, castrated by lateral incision in scrotum, castrated by cap removing (scrotum apex or kept intact (non-castrated. The slaughter of animals occurred in commercial slaughterhouse, at 30 months of age. Non-castrated animals showed higher cold carcass weight (208.0±6.2 kg than the males castrated by different methods (mean 192.0±6.4 kg. There was no difference in subcutaneous fat thickness among the groups, but when the measure was adjusted for carcass weight, there was a higher fat cover in animals castrated with burdizzo (.79± .08 mm/100 kg or lateral incision (.86± .09 mm/100 kg than non-castrated (.61± .05 mm/100 kg. Longissimus dorsi area was higher in noncastrated males (60.47±1.94 cm2 than males castrated with burdizzo tool (50.41±3.18 cm2 . There was not statistical difference for muscle/bone and muscle+fat/bone ratios among the groups, but the muscle/fat ratio was higher in non-castrated animals compared to castrated by cap removing and these were greater than castrated by lateral incision. There was no difference of meat sensorial characteristics, but the marbling score was higher in castrated with burdizzo tool (2.33± .20 points or castrated by cap removing (2.39± .20 points than the non castrated (1.77 ± 0.12 points. Castration method in crossbred dairy cattle males slaughtered with low weight does not promote changes in carcass and meat quality, but noncastrated animals have higher slaughter and cold carcass weights, and higher muscle percentage and muscle / fat ratio than castrated males.

  6. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P;

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity...

  7. Testosterone deficiency: a historical perspective

    OpenAIRE

    Eberhard Nieschlag; Susan Nieschlag

    2014-01-01

    The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial (and other oriental) courts employed castrates as overseers in harems who often obtained high-rank...

  8. Overcoming docetaxel resistance in prostate cancer: a perspective review

    OpenAIRE

    Hwang, Clara

    2012-01-01

    The treatment of metastatic castrate-resistant prostate cancer has been historically challenging, with few therapeutic successes. Docetaxel was the first cytotoxic therapy associated with a survival benefit in castrate-resistant prostate cancer. Toxicity is typical of other cytotoxic agents, with myelosuppression being the dose-limiting toxicity and neurotoxicity also a notable side effect for some patients. Unfortunately, a significant proportion of men with castrate-resistant prostate cance...

  9. 17-Ketosteroids urine test

    Science.gov (United States)

    ... to: Adrenal glands not making enough of their hormones ( Addison disease ) Kidney damage Pituitary gland not making enough of its hormones ( hypopituitarism ) Removal of the testicles (castration)

  10. Perfil hematológico de ratas castradas e intactas induzidas experimentalmente ao hipertireoidismo

    Directory of Open Access Journals (Sweden)

    Carneiro R.A.

    2000-01-01

    Full Text Available The changes of red and white blood cells counts in intact and castrated rats with hyperthyroidism were analysed. A total of 108 five-month-old female Wistar rats, divided into four groups, were used as following: euthyroid castrated, euthyroid intact, hyperthyroid castrated and hyperthyroid intact. Nine animals of each group were killed at 30, 60 and 90 days to evaluate the red and white blood cells counts. The conclusion was that castration or hyperthyroidism did not affect both the red and white blood cells.

  11. Genomics and systems biology of boar taint and meat quality in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Kogelman, Lisette; Meinert, Lene;

    2015-01-01

    , economic losses associated with castrated pigs and a ban on castration in the EU effective by 2018. The main objective of the PhD project is to unravel the underlying mechanisms of BT at the genomic, transcriptomic and phenotypic levels as well as its connection with sensory meat quality (SMQ) in order......Boar taint (BT) is an offensive odour or taste of cooked porcine meat which may occur in entire male pigs due to skatole and androstenone accumulation in the adipose tissue. To avoid BT, surgical castration of young piglets is performed but castration is undesirable due to animal welfare concerns...

  12. Experiment list: SRX286404 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 2374,91.5,46.7,866 GSM1146483: AR Cast1 [caput epididymis, castrated+vehicle]; Mus musculus; ChIP-Seq source..._name=AR_Cast1 || strain=wild type ICR || tissue=caput epididymis || age=8-12 weeks old || treatment=castrated+vehicle

  13. Experiment list: SRX286407 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 19696667,94.8,45.4,7089 GSM1146486: AP2a Cast1a [caput epididymis, castrated+vehicle]; Mus musculus; ChIP-Se...q source_name=AP2a_Cast1a || strain=wild type ICR || tissue=caput epididymis || age=8-12 weeks old || treatment=castrated+vehicle

  14. Experiment list: SRX286394 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 3: AR Cast1 [kidney, castrated+vehicle]; Mus musculus; ChIP-Seq source_name=AR_Cast1 || strain=wild type ICR... || tissue=kidney || age=8-12 weeks old || treatment=castrated+vehicle || chip an

  15. Experiment list: SRX286391 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 7,47.9,41.3,666 GSM1146470: rIgG1a [prostate, castrated+vehicle]; Mus musculus; ChIP-Seq source_name=rIgG1a ...|| strain=wild type ICR || tissue=prostate || age=8-12 weeks old || treatment=castrated+vehicle || chip anti

  16. Experiment list: SRX286398 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 6477: Hnf4a Cast1b [kidney, castrated+vehicle]; Mus musculus; ChIP-Seq source_name=Hnf4a_Cast1b || strain=wi...ld type ICR || tissue=kidney || age=8-12 weeks old || treatment=castrated+vehicle

  17. Experiment list: SRX286408 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 15944359,94.3,40.0,7036 GSM1146487: AP2a Cast1b [caput epididymis, castrated+vehicle]; Mus musculus; ChIP-Se...q source_name=AP2a_Cast1b || strain=wild type ICR || tissue=caput epididymis || age=8-12 weeks old || treatment=castrated+vehicle

  18. Experiment list: SRX286397 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 6476: Hnf4a Cast1a [kidney, castrated+vehicle]; Mus musculus; ChIP-Seq source_name=Hnf4a_Cast1a || strain=wi...ld type ICR || tissue=kidney || age=8-12 weeks old || treatment=castrated+vehicle

  19. Voluntary Genital Ablations: Contrasting the Cutters and Their Clients

    Directory of Open Access Journals (Sweden)

    Robyn A. Jackowich, BA

    2014-08-01

    Conclusions: This study may help identify individuals who are at risk of performing illegal castrations. That information may help healthcare providers protect individuals with extreme castration ideations from injuring themselves or others. Jackowich RA, Vale R, Vale K, Wassersug RJ, and Johnson TW. Voluntary genital ablations: Contrasting the cutters and their clients. Sex Med 2014;2:121–132.

  20. [Hormone treatment of pedophilia].

    Science.gov (United States)

    Vanderschueren, D M

    1997-01-01

    Pedophilia is only one of the sexual deviations that can be treated by chemical castration and it is presently unclear whether pedophilia responds better or worse to this therapy in sexual offenders. Antiandrogens are most often used for chemical castration. With respect to the treatment of sexual deviations, LH-antagonists or the combination of antiandrogens and LH-agonists were not studied very extensively. Long-term effects and side-effects of chemical castration are also presently unclear. Although, there is some indication that recidivism will decrease following chemical castration, its use is limited by a high refusal and drop-out rate. The indications of chemical castration in the treatment of sexual deviation raises important ethical questions.

  1. Efeito da tibolona na morfologia do músculo esquelético, nas enzimas hepáticas e no nível sérico de glicose em ratas castradas Effect of tibolone on the morphology of skeletal muscle, liver enzymes and blood glucose level in castrated female rats

    Directory of Open Access Journals (Sweden)

    Porphirio José Soares Filho

    2012-06-01

    Full Text Available INTRODUÇÃO: O fígado é uma estrutura de elevada complexidade e é fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funções. OBJETIVO: Analisar a influência da tibolona no metabolismo hepático por meio da avaliação de enzimas e metabólitos comumente utilizados em provas de função hepática. MÉTODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4 e tibolona (n = 6, em status de menopausa cirúrgica. A tibolona (1 mg foi administrada diariamente por gavagem durante 20 semanas, com avaliação periódica do peso corporal. Após sedação, efetuou-se coleta de sangue para avaliação bioquímica de albumina (Alb sérica, fosfatase alcalina (FA, transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT], gama-glutamiltranspeptidase (GGT e glicose, mediante espectrofotometria. O músculo esquelético da coxa foi avaliado por histomorfometria em cortes histológicos corados com hematoxilina e eosina (HE. RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alterações musculares esqueléticas e discretas alterações bioquímicas. Além disso, AST e FA estavam diminuídas e GGT estava mais elevada, porém sem significância estatística. A histomorfometria do músculo revelou uma tendência de menor volume celular nesse grupo. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, não interfere de forma significativa nas funções metabólicas e de síntese hepáticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressão genômica da GGT. A tibolona apresenta influência sistêmica associada a menor peso e diminuição da massa muscular e aumento significativo no peso relativo do fígado, além de alteração da glicogenólise hepática e muscular, da gliconeogênese hepática e dos níveis de glicose circulante.INTRODUCTION: The liver is a highly complex structure and it is essential to understand how certain substances may affect its structure and functions. OBJECTIVE: Analyze the influence of tibolone on hepatic metabolism by assessing metabolites and enzymes commonly used in liver function tests. METHODS: Ten Wistar rats in surgical menopausal status were divided into two groups: control (n = 4 and tibolone (n = 6. Tibolone (1 mg was administered by gavage daily for 20 weeks and body weight was periodically assessed. After sedation, blood sampling was performed for biochemical evaluation of serum albumin (Alb, alkaline phosphatase (ALP, transaminases (aspartat aminotranferase and alanine aminotranferase [AST/ALT], gamma glutamyltranspeptidase (GGT and glucose by spectrophotometry. Hematoxylin and eosin-stained histological sections of the skeletal thigh muscle were assessed by histomorphometry. RESULTS: The animals in the tibolone group showed lower body weight, skeletal muscle alterations and slight biochemical changes. In the tibolone group, AST and ALP were decreased GGT was higher, but without a statistically significant difference. The muscle histomorphometry showed that the tibolone group tended to present a lower cell volume. CONCLUSION: Tibolone administered in high doses and for a prolonged period does not interfere significantly neither with liver metabolic functions nor liver synthesis, nor with cell membrane permeability. However, it seems to modulate the genomic expression of GGT. Tibolone has systemic influence on lower body weight, reduced muscle mass, and significant increase in relative liver weight. Additionally, liver and muscular glycogenolysis, liver gluconeogenesis and circulating glucose levels are altered.

  2. Clinical effect of psychological nursing intervention for advanced prostate cancer patients with anxiety and depression after castration surgery%心理护理干预对晚期前列腺癌去势手术后合并焦虑抑郁症患者的临床效果

    Institute of Scientific and Technical Information of China (English)

    郑萍

    2015-01-01

    目的 探讨心理护理干预对晚期前列腺癌去势手术后合并焦虑抑郁症患者的临床效果.方法 选择2012年3月至2014年8月间收治的行去势手术治疗的晚期前列腺癌患者88例,采用随机数字表法分为观察组和对照组,每组44例.对照组患者给予常规护理,观察组患者则在常规护理的基础上给予心理护理干预.护理前后分别行焦虑自评量表(SAS)、抑郁自评量表(SDS)评分并对护理后患者的生活质量进行评估,比较两组结果.结果 两组患者护理后SAS和SDS评分均显著下降,与护理前差异均有统计学意义(P<0.05).观察组患者护理后SAS、SDS评分明显低于对照组,差异有统计学意义(P<0.05).观察组患者治疗后在躯体功能、角色功能、情绪功能、认知功能、社会功能、总体生活质量6个方面的评分均显著高于对照组,差异有统计学意义(P<0.05).结论 心理护理干预可有效减轻晚期前列腺癌去势手术后合并焦虑抑郁症患者的不良情绪,改善患者的预后及生活质量,值得临床推广应用.

  3. 罗伊-纽曼综合模式护理对前列腺癌去势治疗患者心理的影响%Psychological impact of Roy-Newman comprehensive care model on prostate cancer patients with castration

    Institute of Scientific and Technical Information of China (English)

    李雪梅; 周远秀; 张静; 孙英姿

    2010-01-01

    目的:探讨罗伊-纽曼综合模式心理护理对前列腺癌患者术后生活质量和心理状况的影响.方法:将44例前列腺癌围手术期患者随机分为观察组和对照组,观察组应用罗伊-纽曼综合模式进行护理干预,对照组采用常规健康宣教方法进行护理干预.通过生活质量和心理状况问卷调查比较两组患者的生活质量评分值与心理问题发生率.结果:观察组患者生活质量分值明显高于对照组(P<0.05),多项心理问题的发生率明显低于对照组(P<0.05).结论:应用罗伊-纽曼综合模式可有效改善前列腺癌围手术期患者的心理状况,提高其近期生活质量.

  4. 心理干预对老年前列腺癌去势患者术后心理状态的影响%Effect of Psychological Intervention on Mental Status of Elderly Patients with Prostate Cancer and Castration Surgery

    Institute of Scientific and Technical Information of China (English)

    沈玥; 李泓枚; 杨封慧; 张霞; 王毅香

    2015-01-01

    目的:探讨国术期心理干预对老年前列腺癌去势患者心理状况及生活质量的影响.方法:选取2012年6月-2015年1月在我院接受手术治疗的老年前列腺癌患者150例,根据围术期干预方法的不同将所选患者分为研究组和对照组,每组75例.对照组患者给予常规护理干预,研究组在对照组基础上给予心理干预.分别于干预前后应用生活质量核心问卷(QLQ-C30)评价患者生活质量,应用焦虑自评量表(SAS)评价患者焦虑情况,应用抑郁自评量表(SDS)评价患者抑郁情况.结果:干预前,两组患者QLQ-C30、SAS和SDS评分比较均无统计学意义(P>0.05);干预后,两组患者QLQ-C30、SAS和SDS评分均显著优于干预前,组内比较,差异具有统计学意义(P<0.05);干预后,研究组QLQ-C30、SAS和SDS评分优于对照组,两组比较差异具有统计学意义(P<0.05).结论:围术期心理干预对老年前列腺癌去势患者具有较好的干预效果,能够显著改善患者的心理状态,提高术后生活质量.

  5. 盐酸阿扑吗啡片剂对去势大鼠的壮阳作用和生殖器官质量的影响%Effects of Apomorphine Hydrochloride Tablet on Castrated Rats' Vital Function (yang) and the Weight of Their Genital Organ

    Institute of Scientific and Technical Information of China (English)

    符健; 邝少轶; 王世雄

    2003-01-01

    制备雄性去势大鼠模型,测定给药各组去势大鼠阴茎勃起潜伏期和生殖器官质量. 结果表明:与单纯模型组相比,盐酸阿扑吗啡在外部刺激下能提高雄性去势大鼠阴茎的兴奋性,阴茎勃起潜伏期缩短,而给药各组生殖器官的质量和脏器指数与去势大鼠模型组比较均无明显差异.盐酸阿扑吗啡对雄性去势大鼠具有壮阳作用,对生殖器官组织无明显影响.

  6. Influência da castração e da idade de abate sobre as características subjetivas e instrumentais da carne de cordeiros Corriedale Effects of castration and slaughtering age on the subjective and instrumental characteristics of meat from Corriedale lambs

    OpenAIRE

    Eunice de Leon Rota; Maria Teresa Moreira Osório; José Carlos da Silveira Osório; Mauricio Morgado de Oliveira; Mabel Mascarenhas Wiegand; Gilson de Mendonça; Roger Marlon Esteves; Michelle Gonçalves

    2006-01-01

    Este trabalho foi realizado com o objetivo de avaliar o efeito da castração e da idade de abate sobre as características subjetivas e instrumentais da carne de cordeiros Corriedale criados em condições extensivas de pastagem natural. Foram utilizados 60 cordeiros machos (30 não-castrados e 30 castrados) abatidos no ano de 2003, aos 120, 210 e 360 dias de idade, nos meses de fevereiro, maio e outubro, respectivamente. As avaliações da carne foram realizadas no músculo Longissimus dorsi. Pela a...

  7. 高强度聚焦超声对手术去势后前列腺癌患者抗肿瘤免疫功能的影响%How high intensity focused ultrasound affect the body anti-tumor immunity of prostate cancer patients after surgical castration

    Institute of Scientific and Technical Information of China (English)

    徐磊; 王国民; 武睿毅; 张博恒

    2009-01-01

    目的 探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)对中晚期前列腺癌患者手术去势治疗后机体抗肿瘤免疫功能的影响.方法 2007年9月至2008年1月在复旦大学附属中山医院行手术去势治疗的中晚期前列腺癌患者23例随机分为2组,HIFU组为去势手术后行HIFU治疗12例,对照组为单纯去势手术11例.HIFU组平均年龄为(70.92±2.04)岁,初始PSA为(117.75±40.93)ng/mL;对照组平均年龄为(73.27±1.31)岁,初始PSA为(119.44±44.68)ng/mL.所有患者分别于治疗前和治疗后抽取静脉血5 mL,两次抽血时间间隔约6周.检测项目包括CD19+、CD4+CD25+Foxp3+调节性T细胞、VEGF、TGF-β1、IFN-γ和IL-2.HIFU组与对照组治疗前后对照采用Wilcoxon秩和检验(Wilcoxon rank sum test),两组差值对照取对数采用t检验,取P<0.05有统计学差异.结果 HIFU组患者HIFU治疗后TGF-β1(P=0.046)显著降低,CD19+治疗前后无变化,IFN-γ和IL-2较治疗前上升,VEGF较治疗前下降,但均无显著差异.对照组患者去势术后CD4+CD25+Foxp3+调节性T细胞显著上升(P=0.020),CD19+、IFN-γ和IL-2较前下降,VEGF和TGF-β1比治疗前上升,但均无显著差异.HIFU组治疗前后差值与对照组治疗前后差值比较,IL-2(P=0.0151)呈显著上升,CD4+CD25+Foxp3+调节性T细胞(P=0.023 0)、VEGF (P=0.001 7)和TGF-β1(P=0.000 6)呈显著降低.结论 HIFU治疗可在一定程度上提高去势术后前列腺癌患者的机体抗肿瘤功能,其机制可能通过降低机体免疫抑制和分泌免疫促进因子等实现.

  8. High intensity focused ultrasound affect the body anti-tumor immune indexes of intermediate and advanced prostate cancer patients after castration%高强度聚焦超声对中晚期前列腺癌患者去势治疗后机体免疫指标的影响

    Institute of Scientific and Technical Information of China (English)

    吴同胜; 谭卫林; 肖平; 付俊; 吴云

    2014-01-01

    背景与目的:高强度聚焦超声(high intensity focused ultrasound,HIFU)可以有效治疗前列腺癌,但肿瘤是一种全身性的疾病,理想的肿瘤治疗方法是能够在不损伤正常组织的同时进行局部肿瘤切除,还能够激活全身的抗肿瘤免疫反应.本研究旨在探讨HIFU治疗对去势治疗后中晚期前列腺癌患者机体免疫指标的影响.方法:行去势治疗的中晚期前列腺癌患者40例,随机分为2组,HIFU组为去势治疗后2周行HIFU治疗(n=20),对照组为单纯去势治疗(n=20),全部经直肠前列腺穿刺病理检查确诊,均为晚期前列腺癌患者,即前列腺特异性抗原(prostate specific antigen,PSA) >20 ng/mL.患者自愿接受HIFU治疗并签署知情同意书.HIFU组与对照组患者平均年龄(72.56±12.38)岁、(75.23±9.35)岁(P=0.446 3);初始PSA为(105.22±20.55) ng/mL、(100.53±18.38) ng/mL (P=0.451 5).分别取治疗前和治疗后2周前列腺癌患者外周血6d,检测T淋巴细胞亚群(CD4+、CD8+、CD4+/CD8+)和外周血Th细胞因子(IFN-γ、IL-2、IL-4、IL-10).结果:HIFU组患者治疗后CD4+百分比及CD4+/CD8+比值明显升高;细胞因子IFN-γ、IL-2水平明显增高,而IL-4、IL-10水平明显降低,与治疗前相比差异有统计学意义(P<0.05),Th1/Th2平衡向Th1漂移.而对照组患者治疗前、后各项免疫指标差异无统计学意义(P>0.05).HIFU组与对照组前、后各项免疫指标差值比较差异有统计学意义(P<0.05).结论:HIFU治疗可在近期内改善去势治疗后中晚期前列腺癌患者机体免疫功能.

  9. Effect of androgen deprivation on the expression of aquaporins in rat prostate and seminal vesicles.

    Science.gov (United States)

    Tian, J C; Xia, J Y; Jiang, J; Jiang, R; He, Y Z; Lin, H

    2016-04-01

    The aim of this study was to investigate the level of secretions of prostate and seminal vesicles and its association with the expression of AQP0, 1, 4, 5, 6 and 8 in castrated rats. Eight-week-old male Sprague-Dawley (SD) rats (n = 18) were randomly divided into control group, castrated rats group and castrated followed testosterone replacement group. Four weeks after surgery, the secretions and expression of AQP0, 1, 4, 5, 6 and 8 of prostate and seminal vesicles were determined. Serum testosterone was significantly lower in castrated groups than in control and testosterone replacement groups (P seminal vesicle secretions and the expressions of AQP0, 1, 4, 5, 6 and 8 in prostate and seminal vesicles were significantly lower in castrated group than in control and castrated followed testosterone replacement groups (P seminal vesicle secretions in castrated rats may be related to the decrease in AQP0, 1, 4, 5, 6 and 8 in prostatic tissue and seminal vesicles.

  10. Testosterone is required for corticosteroid-binding globulin upregulation by morphine to be fully manifested.

    Science.gov (United States)

    Nock, B; Wich, M; Cicero, T J; O'Connor, L H

    2000-09-01

    We previously reported that morphine increases the concentration of corticosteroid-binding globulin (CBG) in blood of male, but not female, rats. This pronounced sexual dimorphism suggested that CBG upregulation by morphine might be androgen-dependent. In the current studies, we found that castration, whether performed just before or just after puberty or in adulthood, increased the concentration of CBG in adult male rats. Naltrexone did not prevent this increase and, therefore, it does not appear to be attributable to the release of endogenous opioids. Exposure to morphine for 1 week in adulthood increased ( approximately 100%) the concentration of CBG in intact, i.e., sham-castrated, males. The CBG levels of castrated rats treated with morphine did not differ from those of intact rats treated with morphine. However, because castration increased the concentration of CBG, the difference between the placebo and morphine groups decreased with time after castration. At 4 weeks after castration, the difference between the morphine and placebo groups (19%) was no longer statistically significant. Testosterone replacement prevented the rise in CBG levels following castration and maintained the magnitude of the difference between placebo and morphine-treated rats within the normal range. Thus, testosterone appears necessary for morphine effects on CBG to be fully manifested. PMID:11113500

  11. Carcass physical composition and physic-chemical characteristics of meat from Nellore cattle

    Directory of Open Access Journals (Sweden)

    Aline Kellermann de Freitas

    2016-04-01

    Full Text Available Assessment of carcass physical composition and physicochemical characteristics of meat from Nellore males distributed randomly into three treatments: males castrated at 13 months of age at puberty (n=26; castrated at 18 months of age, 15 days before confinement (n=26; and young bulls (n=25. For the evaluation of meat chemical characteristics, we used samples of 12 animals taken at random from each treatment. The experimental design was completely randomized. Animals were slaughtered at 22 months of age after 100 days of confinement. The carcasses of young bulls showed higher contents of muscle (66.46 % and bone (16.03 %, and lower fat content (17.66 %, in relation to that of steers castrated at 13 (62.83,15.28, and 22.11 %, respectively or 18 months (63.99, 15.29, and 21.53%, respectively, which did not differ amongst themselves. The meat of young bulls was darker (3.07 points than the meat from those castrated at 13 months of age (3.43 points, while the meat from those castrated at 18 months displayed an intermediate color (3.29 points, not differing from the others. Young bulls yielded meat with lower content of intramuscular fat (3.18 points and lipids (3.81% in relation to those castrated at 13 (4.58 points and 6.77%, respectively or 18 months (4.52 points and 5.66%, respectively. Protein content was higher (P 0.05 by the age of castration, with young bulls having lower values in relation to the castrated males. Castration of Nellore young bulls in early puberty increases the edible portion of the carcass due to the higher body fat deposit.

  12. The effects of a slow release GnRH agonist implant on male rabbits

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

    2015-01-01

    Surgical castration is done in male pet rabbits for reproduction control, to reduce inter-male aggression and to control hyper-sexuality, territory marking and aggression against humans. Alternatives to surgical castration are requested because of a relatively great anaesthetic risk in rabbits....... Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...

  13. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P;

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity...... with a larger number of patients and a longer follow-up will contribute more to the overview's results....

  14. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    DEFF Research Database (Denmark)

    Kaisary, A V; Iversen, P; Tyrrell, C J;

    2001-01-01

    Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non...... with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203....

  15. A Dose-Finding Study of OTX105/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)

    Science.gov (United States)

    2016-07-27

    NUT Midline Carcinoma; Triple Negative Breast Cancer; Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation; Castrate-resistant Prostate Cancer (CRPC); Pancreatic Ductal Adenocarcinoma

  16. [Role of urologists in the era of new treatment modalities for CRPC in Japan].

    Science.gov (United States)

    Ozono, Seiichiro

    2014-07-01

    New medical treatment modalities for castration resistant prostate cancer(CRPC), including hormonal therapy and chemotherapy, will be approved in Japan. Here, we discuss the management of these new treatment strategies by urologists. PMID:25131867

  17. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

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

  18. Influence of testosterone on the distribution of 65Zn-binding proteins in the prostate and seminal vesicles of rats

    International Nuclear Information System (INIS)

    65Zn (7.4 MBq; 200 μCi) was injected intravenously into normal, castrated and castrated, testosteronesubstituted rats. After 1,24 and 48 hours, the distribution of 65Zn-binding proteins in the 100,000 g supernatant of the prostate and seminal vesicles was investigated by separation on Sephadex G 100. The prostate and seminal vesicles from any one rat showed the same distribution pattern of 65Zn-proteins. In castrated rats, the incorporation of 65Zn was, however, 5-6 times lower than in the normal or castrated, testosterone-substituted rats. One hour after the injection, the highest activity of 65Zn was found in proteins in the molecular weight range above 100,000. After 48 hours the greatest proportion of 65Zn was present in the protein peak corresponding to 28,000 Daltons. (orig.) 891 AJ

  19. Antiandrogen monotherapy

    DEFF Research Database (Denmark)

    Kolvenbag, G J; Iversen, P; Newling, D W

    2001-01-01

    Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quali...

  20. Antiandrogen monotherapy: indications and results

    DEFF Research Database (Denmark)

    Iversen, Peter

    2002-01-01

    Many patients with prostate cancer for whom hormonal therapy is indicated are still physically and sexually active; quality of life is therefore a vital issue when considering treatment options. Traditional castration-based therapies, although effective, have implications with respect to quality...... of life, causing loss of libido, impotence, fatigue, and reduced bone mineral density. Monotherapy with a nonsteroidal antiandrogen is an attractive therapeutic alternative to castration, offering effective therapy with potential quality-of-life benefits. Of the available nonsteroidal antiandrogens...... with castration, in terms of sexual interest and physical capacity, in patients with either M0 and M1 stage disease. Data from a small subgroup of patients with stage M0 disease suggest that bicalutamide may also reduce the risk of osteoporosis compared with castration. Long-term therapy with bicalutamide 150-mg...

  1. Radium-223 for Advanced Prostate Cancer

    Science.gov (United States)

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

  2. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

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

    Science.gov (United States)

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

  4. Male Rat Susceptibility for Liver and Kidney Injury

    Directory of Open Access Journals (Sweden)

    Sarkawt H. Hamad

    2016-04-01

    Full Text Available The experimental study of this paper was designed to investigate male rat susceptibility to liver injury. A combination of two experimental animal models (Lead acetate for tissue injury (80 mg / L and castration had been used on twenty male rats, they were divided into two groups sham (n = 10; castrated (n = 10. Results revealed that, liver weight reduced significantly (P < 0.05 in sham group in comparison with castrated rats, but kidney weight changed slightly. Also, serum aminotransferase (AST was significantly higher in sham versus castrated rats. Neither alanine aminotransferase (ALT and alkaline phosphatase (ALP nor malondialdehyde (MDA changed. In conclusion, the absence of male sex hormone would delay tissue injury of male rat organs especially liver organ.

  5. Use of early chemotherapy for hormone-sensitive prostate cancer: time for CHAARTED

    OpenAIRE

    Aragon-Ching, Jeanny B.

    2015-01-01

    CHAARTED was an ECOG-led phase III trial looking at early chemotherapy with the use of docetaxel in addition to androgen deprivation therapy (ADT) versus ADT alone in hormone-sensitive prostate cancer. The positive results of the trial showing marked improvement in overall survival in those who received chemotherapy with ADT have revolutionized the treatment of metastatic castration-sensitive prostate cancer. In addition to overall survival, secondary endpoints such as time to castration resi...

  6. In house validation of a reference method for the determination of boar taint compounds by LC-MSMS

    OpenAIRE

    Buttinger, Gerhard; KARASEK LUBOMIR; VERLINDE PHILIPPE; Wenzl, Thomas

    2014-01-01

    Meat from male pigs may develop an off-flavour, commonly known as boar taint. For that reason male piglets are surgically castrated at young age to avoid the potential off-flavour formation. Animal welfare concerns have triggered research into alternatives to surgical castration of male piglets with the long-term goal of abandoning it by 1 January 2018. The ALCASDE study has shown that the agreement of testing results for androstenone and skatole in pig fat produced in several laborato...

  7. Inter-laboratory validation of a reference method for the determination of boar taint compounds by GC-MS and LC-MSMS

    OpenAIRE

    Buttinger, Gerhard; Wenzl, Thomas

    2014-01-01

    Meat from male pigs may develop an off-flavour, commonly known as boar taint. For that reason male piglets are surgically castrated at young age to avoid the potential off-flavour formation. Animal welfare concerns have triggered research into alternatives to surgical castration of male piglets with the long-term goal of abandoning it by 1 January 2018. The ALCASDE study has shown that the agreement of testing results for androstenone and skatole in pig fat produced in several laborato...

  8. Energy Requirements in Early Life Are Similar for Male and Female Goat Kids

    OpenAIRE

    Bompadre, T. F. V.; Neto, O. Boaventura; Mendonca, A. N.; Souza, S. F.; D. Oliveira; Fernandes, M. H. M. R.; Harter, C. J.; Almeida, A. K.; Resende, K. T.; Teixeira, I. A. M. A.

    2014-01-01

    Little is known about the gender differences in energetic requirements of goats in early life. In this study, we determined the energy requirements for maintenance and gain in intact male, castrated male and female Saanen goat kids using the comparative slaughter technique and provide new data on their body composition and energy efficiency. To determine the energy requirements for maintenance, we studied 21 intact males, 15 castrated males and 18 females (5.0±0.1 kg initial body weight (BW) ...

  9. The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer

    OpenAIRE

    Shaw, Greg L; Whitaker, Hayley; Corcoran, Marie; Dunning, Mark J.; Luxton, Hayley; Kay, Jonathan; Massie, Charlie E; Miller, Jodi L.; Lamb, Alastair D.; Ross-Adams, Helen; Russell, Roslin; Adam W Nelson; Eldridge, Matthew D.; Lynch, Andrew G.; Ramos-Montoya, Antonio

    2016-01-01

    The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tum...

  10. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth.

    Science.gov (United States)

    Santanam, Urmila; Banach-Petrosky, Whitney; Abate-Shen, Cory; Shen, Michael M; White, Eileen; DiPaola, Robert S

    2016-02-15

    Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer. PMID:26883359

  11. [Metastatic hormone-sensitive prostate cancer].

    Science.gov (United States)

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

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

  12. Effects of testosterone on expression of insulin-like growth factor 1 in cartilage of knee joints with osteoarthritis in male rabbits%睾酮干预雄兔膝骨关节炎软骨中胰岛素样生长因子1的表达

    Institute of Scientific and Technical Information of China (English)

    吴术红; 刘毅; 熊华章; 邹刚

    2011-01-01

    BACKGROUND: The effects of testosterone on osteoarthritis (OA) remain controversial. The regulatory effects of testosterone on cartilage metabolism have been rarely reported. OBJECTIVE: To investigate the effects of testosterone on insulin-like growth factor 1 (IGF-1) expression in cartilage of knee joints with osteoarthritis in male rabbits. METHODS: Twenty-four male rabbits were established into OA models with Hulth method on the right knee joints and then randomly divided into four groups: non-castrated, castrated, testosterone and model. In the non-castrated group, testis was not removed. In the other three groups, bilateral testes were removed. At the end of the 8th week, rabbits in the non-castrated group and castrated for 8 weeks group were sacrificed for sample harvesting. From the 9th week, physiological dose of testosterone undecanoate (6 mg/kg, once every 2 weeks) was intramuscularly injected into the rabbits from the testosterone group. The castrated for 16 weeks group rabbits were normally raised. At the end of 16th week, rabbits from the testosterone and castrated for 16 weeks groups were sacrificed for sample harvesting. RESULTS AND CONCLUSION: Gross and histological observation results showed that the lesion degree of knee joint cartilage was more severe in the non-castrated group than in the castrated group, in the testosterone group than in the castrated for 16 weeks group, but there was no obvious difference between castrated for 8 weeks group and castrated for 16 weeks group. Immunohistochemistry results showed that IGF-1 expression was observed in the knee joint cartilage of all rabbits. IGF-1-positive cells were significantly more in the non-castrated group than in the castrated for 8 weeks group (P 0.05). These findings suggest that testosterone can postpone cartilage degeneration by up-regulating IGF-1 expression in knee joint cartilage of castrated male rabbits.%背景:睾酮对骨关节炎的作用尚无一致的观点,其调节软骨代

  13. Changes in quality of goat meat after alterations in animal Handling - doi:10.5020/18061230.2007.p33

    Directory of Open Access Journals (Sweden)

    Frederico José Beserra

    2012-01-01

    Full Text Available This study aimed at evaluating the effect of animal handling, consisting in castration and cashew nut diet supplementation, on the cholesterol content and percentage composition of the muscles that constitute the leg meat cut from crossbred goats, grown in Ceará State. A case experimental design was applied with twenty male-animals with 5-6 months age and mean weight of 12 Kg, randomly divided in two groups of castrated (10 and intact (10 animals. In individual bays, they received during 5 months, two food regimen based on dried elephant grass (Pennisetum purpureum and a standard isoproteic ration (corn and soy oil, one of them with the addition of 13% cashew nut bran (CNB, forming four sub-groups: A1 (intact with no CNB supplemented diet; A2 (intact with CNB supplemented diet; B1 (castrated with no CNB supplemented diet and B2 (castrated with CNB supplemented diet. The castration associated with the CNB supplementation increased the meat’s fat yield from 1.16% to 3.57% and the cholesterol content from 36.47 mg/100g to 62.30 mg/100g. The ash yield decreased from 1.14% to 1.04%. The castration isolated only reduced moisture yield from 75.98% on sub-group A2 to 74.19% on sub-group B2. In intact animals that fed diet supplemented with CNB the protein decreased from 20.58% to 18.85% (P < 0.05 (sub-groups A1 and A2. The increased cholesterol content was highly correlated with the increase of the fat (93% In conclusion, these results showed that the combined use of castration and cashew nut bran (13% diet negatively influenced the dietetic and nutritional quality of goat leg meat.

  14. The Practice of Scottish Urologists in the Assessment and Management of Fracture Risk in the Ageing Male being Treated for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Wee Sing Ngu

    2007-01-01

    Full Text Available The aim of this study was to ascertain the practice of urologists in Scotland in the assessment and prevention of fracture risk in males starting castration-type therapy for prostate cancer. A questionnaire survey was sent to all practicing consultant urologists in Scotland. A majority of urologists, 25 (64.1%, did not consider the state of their patients' bone mineral density (BMD before commencing castration-type therapy. The rest used various methods to assess BMD, including clinical impression alone, plain bone radiographs, and dual-energy X-ray absorptiometry (DEXA. Various methods were used in the prophylaxis and treatment of osteoporosis, including avoidance of castration type therapy and the use of bisphosphonates and bicalutamide along with castration-type therapy. This study has shown that there is no consensus as to the assessment and management of fracture risk in patients with prostate cancer commencing or on established castration-type therapy. The situation needs to be addressed with some consensus guidance.

  15. Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference.

    Science.gov (United States)

    Pavón, Natalia; Martínez-Abundis, Eduardo; Hernández, Luz; Gallardo-Pérez, Juan Carlos; Alvarez-Delgado, Carolina; Cerbón, Marco; Pérez-Torres, Israel; Aranda, Alberto; Chávez, Edmundo

    2012-10-01

    In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined. At the mitochondrial level respiratory control, transmembranal potential and calcium management were determined; Western blot of some mitochondrial components was also performed. Alterations in cardiac function were worst in intact males and castrated females as compared with those found in intact females and castrated males, cytokine levels were modulated also by hormonal status. Regarding mitochondria, in those obtained from hearts from castrated females without ischemia-reperfusion, all evaluated parameters were similar to those observed in mitochondria after ischemia-reperfusion. The results show hormonal influences on the heart at functional and mitochondrial levels. PMID:22609314

  16. [Urinary incontinence and puppy coat due to spaying in the bitch. An overview of pathophysiology, diagnosis and therapy].

    Science.gov (United States)

    Reichler, I M

    2010-06-01

    Urinary incontinence as a consequence of an insufficient urethral closure mechanism (urethral sphincter mechanism incompetence, USMI) or an impaired storing capacity of the urinary bladder is a considerable side effect of castration in the female dog. Different factors such as breed, body weight and time of spaying have an impact on the risk of urinary incontinence. Loss of urine while the patient is recumbent is the most typical symptom which is first observed at a mean time of 2.8 years after castration. Diagnosis is obtained by excluding other causes, whereas a precise patient history is particularly helpful. Therapy is aimed at increasing the closing pressure of the urethra and/or the compliance of the urinary bladder. Usually success can be achieved by medical therapy, thus surgical intervention is normally not required. In addition to urinary incontinence, coat changes can be observed as an undesirable effect of castration in certain dog breeds. To date, the pathophysiology of decreased urethral closing pressure, altered storing function of the urinary bladder and coat changes induced by castration are still not fully understood. Apart from the well-known hypothesis of estrogen deficiency, altered secretion of the hypothalamic and pituitary hormones GnRH, FSH and LH due to castration may have an influence. In addition to a-adrenergic medication, Flavoxate and Estriol, depot formulations of GnRH analogues have been successfully used to treat urinary incontinence. These depot formulations have also been described for the treatment of coat changes due to spaying. PMID:22290549

  17. Androgens increase lws opsin expression and red sensitivity in male three-spined sticklebacks.

    Directory of Open Access Journals (Sweden)

    Yi Ta Shao

    Full Text Available Optomotor studies have shown that three-spined sticklebacks (Gasterosteus aculeatus are more sensitive to red during summer than winter, which may be related to the need to detect the red breeding colour of males. This study aimed to determine whether this change of red light sensitivity is specifically related to reproductive physiology. The mRNA levels of opsin genes were examined in the retinae of sexually mature and immature fish, as well as in sham-operated males, castrated control males, or castrated males implanted with androgen 11-ketoandrostenedione (11 KA, maintained under stimulatory (L16:D8 or inhibitory (L8:D16 photoperiods. In both sexes, red-sensitive opsin gene (lws mRNA levels were higher in sexually mature than in immature fish. Under L16:D8, lws mRNA levels were higher in intact than in castrated males, and were up-regulated by 11 KA treatment in castrated males. Moreover, electroretinogram data confirmed that sexual maturation resulted in higher relative red spectral sensitivity. Mature males under L16:D8 were more sensitive to red light than males under L8:D16. Red light sensitivity under L16:D8 was diminished by castration, but increased by 11 KA treatment. Thus, in sexually mature male sticklebacks, androgen is a key factor in enhancing sensitivity to red light via regulation of opsin gene expression. This is the first study to demonstrate that sex hormones can regulate spectral vision sensitivity.

  18. Carcass and meat quality characteristics of Brahman cross bulls and steers finished on tropical pastures in Costa Rica.

    Science.gov (United States)

    Rodriguez, Julio; Unruh, John; Villarreal, Milton; Murillo, Olger; Rojas, Sailim; Camacho, Jorge; Jaeger, John; Reinhardt, Chris

    2014-03-01

    Forty-eight male calves (3/4 Brahman×1/4 Charolais) were used to determine carcass cutability and meat tenderness of Longissimus lumborum (LL), Gluteus medius (GM), Semitendinosus (ST) and Psoas major (PM) steaks from lighter weight carcasses of bulls and steers castrated at 3, 7, or 12 mo of age grown under tropical pasture conditions. Steaks from steers had lower (more tender) LL Warner-Bratzler shear force (WBSF) values than those from bulls. Steaks from steers castrated at 3 mo had lower GM WBSF than those from bulls. For PM steaks, those aged 28 d had lower WBSF than those aged 2d. Steaks aged 28 d had the lowest LL and GM WBSF and steaks aged 2d had the highest LL, GM, and ST WBSF. Castration at younger ages is recommended because it provides improvement in LL and GM tenderness over bulls with no differences in carcass traits or subprimal yields. PMID:24342184

  19. Trenbolone acetate induced changes in the genital tract of male pigs.

    Science.gov (United States)

    López-Bote, C; Sancho, G; Martínez, M; Ventanas, J; Gázquez, A; Roncero, V

    1994-03-01

    Eleven entire and twelve castrated male pigs were implanted with trenbolone acetate and the effects of the treatment on genital tract macro- and microscopical modifications were evaluated and compared to non-implanted animals. In entire male pigs a reduction of testicular weight and size was observed as a consequence of the treatment (< 0.001), but no important modifications were found in bulbourethral gland and seminal vesicles macroscopically. Castrated non-implanted males had bulbourethral gland atrophy (P < 0.01), while castrated implanted ones showed similar development to entire males. As for vesicular glands there were no significant differences among the four groups under study. Histological study of prostate has demonstrated structural modifications. As a consequence of the treatment glandular lumen was increased (P < 0.05), and most parenchyma was occupied by polymorphous cysts.

  20. Parthenocarpie naturelle chez la tomate. II: Etude d'une collection varietale

    OpenAIRE

    Philouze, J.

    1985-01-01

    L’étude a porté sur 10 variétés pour juger de leur aptitude à la parthénocarpie naturelle, ainsi que sur une variété témoin non parthénocarpique, « Monalbo ». Quatre essais ont été réalisés en culture de printemps sous serre verre chauffée, avec floraison en mars-avril. Deux traitements ont été appliqués : d’une part castration des fleurs, non suivie de pollinisation ; d’autre part pollinisation, soit manuelle après castration, soit naturelle sans castration. On a effectué l’étude comparé...

  1. Influence of social mixing and group size on skin lesions and mounting in organic entire male pigs

    DEFF Research Database (Denmark)

    Thomsen, Rikke; Edwards, Sandra A; Rousing, Tine;

    2016-01-01

    , hypothesising that procedures that disrupt the social stability (e.g. regrouping) will have a larger negative effect in small groups compared with large groups. Approximately 1600 organic entire male pigs of the breed (Landrace×Yorkshire)×Duroc were reared in parallel in five organic herds, distributed across......Alternatives to surgical castration are needed, due to stress and pain caused by castration of male pigs. One alternative is production of entire male pigs. However, changed behaviour of entire males compared with castrated males might adversely affect the welfare of entire males and changes...... in management procedures and production system might be needed. Elements from the organic pig production system might be beneficial in this aspect. The aim of this article is to investigate the effect of grouping strategy including social mixing and group size on levels of mounting behaviour and skin lesions...

  2. Carcass and meat quality characteristics of Brahman cross bulls and steers finished on tropical pastures in Costa Rica.

    Science.gov (United States)

    Rodriguez, Julio; Unruh, John; Villarreal, Milton; Murillo, Olger; Rojas, Sailim; Camacho, Jorge; Jaeger, John; Reinhardt, Chris

    2014-03-01

    Forty-eight male calves (3/4 Brahman×1/4 Charolais) were used to determine carcass cutability and meat tenderness of Longissimus lumborum (LL), Gluteus medius (GM), Semitendinosus (ST) and Psoas major (PM) steaks from lighter weight carcasses of bulls and steers castrated at 3, 7, or 12 mo of age grown under tropical pasture conditions. Steaks from steers had lower (more tender) LL Warner-Bratzler shear force (WBSF) values than those from bulls. Steaks from steers castrated at 3 mo had lower GM WBSF than those from bulls. For PM steaks, those aged 28 d had lower WBSF than those aged 2d. Steaks aged 28 d had the lowest LL and GM WBSF and steaks aged 2d had the highest LL, GM, and ST WBSF. Castration at younger ages is recommended because it provides improvement in LL and GM tenderness over bulls with no differences in carcass traits or subprimal yields.

  3. Testosterone does not influence opiate binding sites in the male rat brain.

    Science.gov (United States)

    Cicero, T J; Newman, K S; Meyer, E R

    1983-09-26

    It has been reported previously that castration produces testosterone-reversible increases in the density of 3H-naltrexone binding sites in the male rat brain. Unfortunately, we were unable to replicate these observations in a comprehensive series of studies. Specifically, we found that castration failed to produce changes in the Kd or Bmax of opiate binding sites in whole male rat brain, or in the hypothalamus, utilizing 3H-dihydromorphine (a mu receptor ligand), 3H-D-alanine, D-leucine enkephalin (delta) or 3H-naltrexone (ubiquitous). Furthermore, we found that the relative proportion of mu and delta binding sites in brain was unchanged by castration. The reasons for the discrepancy between the present results and those previously reported are unclear, but it appears that the provocative hypothesis that testosterone influences opioid receptors in brain must be carefully reevaluated. PMID:6310295

  4. [The development of therapeutics targeting oxidative stress in prostate cancer].

    Science.gov (United States)

    Shiota, Masaki; Yokomizo, Akira; Naito, Seiji

    2014-12-01

    Oxidative stress is caused by increased reactive-oxygen species (ROS) due to augmented ROS production and impaired anti-oxidative capacity. Recently, oxidative stress has been revealed to promote castration resistance via androgen receptor(AR)-dependent pathway such as AR overexpression, AR cofactor, and AR post-translational modification as well as AR-independent pathway, leading to the emergence of castration-resistant prostate cancer (CRPC). Therefore, antioxidants therapy using natural and chemical ROS scavengers and inhibitors of ROS production seems to be a promising therapy for CRPC as well as preventing castration resistance. However, at present, the application to therapeutics is limited. Therefore, further research on oxidative stress in prostate cancer, as well as on the development for clinical application would be needed.

  5. The Ritualized Bodies of Cybele's Galli and the
 Methodological Problem of the Plurality of Explanations

    Directory of Open Access Journals (Sweden)

    J. Peter Södergård

    1993-01-01

    Full Text Available The explanandum in this article is the self-castration of Cybele's Galli. The explanans is the various theories that have been put forward to elucidate this phenomenon. The author begins by sketching out the complicated religio-historical scene for this ritual, then introduces the plurality of theories concerning Galli's ritual self-castration, so that the intellectual dilemma of evaluation and preference is obvious; which one of the theories is decisive? Are they necessary or sufficient? Do they compete or cooperate? The aim of this article is also to make a critical methodological evaluation of the use of psychological determinants in religio-historical studies of the self-castration of the Galli in the cult of Cybele and Attis.

  6. Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation

    International Nuclear Information System (INIS)

    Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supra additive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supra additive effect when the combination was used. Discussion: A supra additive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supra additive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and

  7. Protection of estrogen in portal hypertension gastropathy: an experimental model

    Directory of Open Access Journals (Sweden)

    Maria Isabel Morgan-Martins

    2011-09-01

    Full Text Available CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO; intact (I with partial portal vein ligation (I + PPVL, castrated (C and castrated with partial ligation of the vein (C + PPVL. Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE, and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

  8. Regulatory mechanisms for the development of the migratory phenotype: roles for photoperiod and the gonad.

    Science.gov (United States)

    Ramenofsky, Marilyn; Németh, Zoltán

    2014-06-01

    This article is part of a Special Issue "Energy Balance". Male white-crowned sparrows, Zonotrichia leucophrys gambelii, were studied to investigate roles of natural day length and the testes in regulating development and expression of the vernal migration phenotype. Previous work suggested that a pulse of androgen during winter months followed by the vernal increase in photoperiod promotes fueling (fat deposition) to support long distance flight; however, other traits required for successful migration remain untested. To investigate these points, birds were captured on their wintering grounds and castrated prior to winter solstice following Mattocks (1976). A subset of the castrates received 8mm Silastic implants of testosterone (T-castrates) and others blank implants (Blank-castrates) for 16 days in February. Shams were surgical controls. Migratory traits measured were as follows: 24h locomotor activity, prenuptial molt, body mass, fat score, flight muscle profile, cloacal protuberance (CPL) and plasma androgens measured over 28 weeks divided into 3 experimental periods (pre-implant, implant, and post-implant). Under short day lengths, castration increased diurnal locomotor activity over Shams. Testosterone implants temporarily enhanced CPL, plasma androgens and flight muscle enlargement, but failed to induce migratory restlessness. Whereas all groups exhibited seasonal increases in mass, fat score and muscle profile, only Shams showed timely onset and completion of prenuptial molt and migratory restlessness. Thus, for castrated males exposed to naturally increasing day lengths, the organizational effects of a transient testosterone surge were not sufficient to actuate a timely spring molt and migratory behavior. A fully functional testis that can organize central processes is required for the entire expression of the spring migratory phenotype. PMID:24780144

  9. [Castrati--everything to achieve fame].

    Science.gov (United States)

    Hatzinger, M; Vöge, D; Sold, M; Sohn, M

    2009-06-01

    The phenomenon of castration is wedded to the baroque era. This epoch stands for pure sensual pleasure. Those who could afford it tried to arrange their earthly days to be as enjoyable as possible. A perverse bloom of this ambition was the angel-like voices of the castrati. The supernatural sound of the voice was meant to let the opera visitors escape into another world. High society was almost addicted to those voices. On the other hand nobody showed any interest in the spiritual life of the castrati. Farinelli, Nicolini, and Senesino, three of the most famous castrati, were the first musical superstars of the eighteenth century. Their voices moved the decadent baroque audience to tears and enraptured them to the point of standing ovations. But the price for this fame was high. Only through castration in their early boyhood could this bell-like voice be kept. Because of the sensational success of the castrati, a huge wave of castration swept over Italy. Ambitious parents had their boys castrated, hoping that they would also become famous opera stars. It is estimated that in Italy alone over half a million boys were victims of this mutilating procedure during the eighteenth century. Because castration was officially forbidden it was done"behind closed doors" by untrained barbers and of course was associated with a high morbidity and mortality rate. The height of the castrati ended with the fading eighteenth century. The last castrato, Alessandro Moreschi, was engaged as a chorister and soloist at the Sistine Chapel in the Vatican. He was pensioned off by Pope Pius X in the year 1912 after an official ban on castrated singers was imposed. With that a very impressive part of music history had ended. PMID:19333571

  10. Carcass characteristics of feedlot-finished Zebu and Caracu cattle

    Directory of Open Access Journals (Sweden)

    Flávio Dutra de Resende

    2014-02-01

    Full Text Available This study analyzes the chemical carcass characteristics and carcass losses in 86 cattle, both castrated and non-castrated, with an average initial weight of 329 kg and an average age of approximately 20 months, including 12 Gyr, 20 Guzerat, 20 Nellore, and 20 Caracu among the herds selected for weight determination at 378 days of age, as well as 14 Nellore cattle that were not selected. The diet contained a roughage-to-concentrate ratio of 60:40 in terms of dry matter (DM, with 14.8% crude protein as a percentage of DM and corn silage as roughage. A completely randomized 5 × 2 factorial experimental design was used, including five breeds and two sex classes. The following values were determined: losses due to the trimming of commercial cuts and cooking; shear force; the temperature and pH of the meat; and the chemical composition of the Hankins and Howe section (HH section. The castrated animals exhibited greater losses from the front trimmings compared with the non-castrated cattle. There were no differences in the final pH values of the carcasses among the breeds, although the noncastrated animals exhibited higher values than the castrated ones, likely because non-castrated animals were more susceptible to stress. The final pH remained within the range considered optimal for all of the carcasses studied. No differences were observed in the shear force among the breeds or between the two sexes. When appropriately managed, zebu breeds are capable of producing tender meat, thus meeting the demands of the consumer market.

  11. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

    Directory of Open Access Journals (Sweden)

    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  12. Genes regulated by androgen in the rat ventral prostate

    OpenAIRE

    Wang, Zhou; Tufts, Rachel; Haleem, Riffat; Cai, Xiaoyan

    1997-01-01

    Genes that are regulated by androgen in the prostate were studied in the rat. Four of the less than 10 genes that are down-regulated by androgen in the ventral prostate of a 7-day castrated rat were identified; their mRNAs decayed with identical kinetics. Twenty-five of the estimated 56 genes that are up-regulated by androgen in the castrated prostate have been isolated. The up-regulated genes fall into two kinetic types. Early genes are significantly up-regulated by 6.5 hr whereas the delaye...

  13. A phytosterol enriched refined extract of Brassica campestris L. pollen significantly improves benign prostatic hyperplasia (BPH) in a rat model as compared to the classical TCM pollen preparation Qianlie Kang Pule'an Tablets.

    Science.gov (United States)

    Wang, Ruwei; Kobayashi, Yuta; Lin, Yu; Rauwald, Hans Wilhelm; Fang, Ling; Qiao, Hongxiang; Kuchta, Kenny

    2015-01-15

    In Qinghai Province, the Brassica campestris L. pollen preparation Qianlie Kang Pule'an Tablet (QKPT) is traditionally used for BPH therapy. However, in QKPT the content of supposedly active phytosterols is relatively low at 2.59%, necessitating high doses for successful therapy. Therefore, a phytosterol enriched (4.54%) refined extract of B. campestris pollen (PE) was developed and compared with QKPT in a BPH rat model. Six groups of rats (n=8 each), namely sham-operated distilled water control, castrated distilled water control, castrated QKPT 2.0g/kg, castrated PE 0.1g/kg, castrated PE 0.2g/kg, and castrated PE 0.4g/kg, were intragastrically treated with the respective daily doses. Testosterone propionate (0.3mg/day) was administered to all castrated rats, while the sham-operated group received placebo injections. After 30 days, the animals were sacrificed and prostates as well as seminal vesicles excised and weighted in order to calculate prostate volume index (PVI) as well as prostate index (PI) and seminal vesicle index (SVI), defined as organ weight in g per 100g body weight. Compared with sham-operated controls, PI (p<0.01), PVI (p<0.01), and SVI (p<0.01) were all significantly increased in all castrated, testosterone treated rats. After treatment with PE at 0.4 and 0.2g/kg or QKPT at 2.0g/kg per day, both indices were significantly reduced (p<0.01) as compared to the castrated distilled water control. For PE at 0.1g/kg per day only PI was significantly reduced (p<0.05). At the highest PE concentration of 0.4g/kg per day both PI and SVI were also significantly reduced when compared to the QKPT group (p<0.05). Both PE and QKPT demonstrated curative effects against BPH in the applied animal model. In its highest dose at 0.4g/kg per day, PE was clearly superior to QKPT.

  14. Chemotherapy in Prostate Cancer.

    Science.gov (United States)

    Hurwitz, Michael

    2015-10-01

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

  15. Effects of Plagiorchis elegans (Digenea: Plagiorchiidae) infection on the reproduction of Biomphalaria glabrata (Pulmonata: Planorbidae).

    Science.gov (United States)

    Zakikhani, M; Rau, M E

    1998-10-01

    Infection with the digenean parasite Plagiorchis elegans dramatically reduced the reproductive output of Biomphalaria glabrata exposed to the parasite as juveniles or adults. The total number of eggs produced by infected snails was reduced to approximately 7 and 13% of control values, respectively. Parasitic castration was attributed to the presence of mother sporocysts that readily established in the tissues of this incompatible host. Infection did not result in the production of cercariae but significantly shortened the life span of juvenile and adult B. glabrata by approximately 23 and 10%, respectively. Plagiorchis elegans also castrated its compatible host, Stagnicola elodes. PMID:9794632

  16. Effects of Dietary Thiazolidinedione Supplementation on Growth Performance, Intramuscular Fat and Related Genes mRNA Abundance in the Longissimus Dorsi Muscle of Finishing Pigs

    OpenAIRE

    Chen, X; Feng, Y.; Yang, W. J.; Shu, G.; Jiang, Q. Y.; X. Q. Wang

    2013-01-01

    The objective of this study was to investigate the effect of dietary supplementation with thiazolidinedione (TZD) on growth performance and meat quality of finishing pigs. In Experiment 1, 80 castrated finishing pigs (Large White×Landrace, BW = 54.34 kg) were randomly assigned to 2 treatments with 5 replicates of 8 pigs each. The experimental pigs in the 2 groups were respectively fed with a diet with or without a TZD supplementation (15 mg/kg). In Experiment 2, 80 castrated finishing pigs (L...

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  19. A variation on Freud's theme in "A child is being beaten"--mother's role: some implications for superego development in women.

    Science.gov (United States)

    Lax, R F

    1992-01-01

    Clinical material is presented leading to a discussion of beating fantasies which varies from Freud's model. Analysis shows that the fantasied role girls assign to mother as the punisher in the oedipal drama is equivalent to the fantasied role boys ascribe to father as castrator. For both sexes, castration anxiety spurs the internalization of parental prohibitions, the repression of oedipal wishes, and the subsequent structuralization of the superego. Mother establishes the "oedipal law" for the girl analogously to father's doing the same for the boy. The role that such fantasies play in the formation of the female superego is examined. PMID:1593080

  20. Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits model

    International Nuclear Information System (INIS)

    Previous clinical and experimental studies suggest that androgens could have adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zeland white male rabbits was realized. 20 rabbits underwent orchidectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. Castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. Castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic plaque formation. Results: animals that had a normal diet (n=20) had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet of 429.2 ± 262.0 mg/dl (p< 0.001). Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/ml and in the castrated were 0.8 ± 0.4 ng/ml (p= 0.024). In non-castrated rabbits the effect of hypercholesterolemia (366 ± 226.1 mg/dl) inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dl (p <0.001) and severe morphological changes such as plaque area 2.6 ± 2.3mm (p <0.001), vessel plaque/area 0.25 ± 0.1 (p <0.001) and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001). Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS) and endothelium dependent relaxation was 38.5 ± 201% (p = 0.03). Conclusion: This study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe

  1. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  2. [Prostate cancer stem cells: advances in current research].

    Science.gov (United States)

    Wu, Gang; Wu, Deng-long

    2015-02-01

    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  3. Liposomal nanomedicines in the treatment of prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Metselaar, Josbert M; Storm, G; van der Pluijm, Gabri

    2014-01-01

    Prostate cancer is the most common cancer type and the second leading cause of death from cancer in males. In most cases, no curative treatment options are available for metastatic castration-resistant prostate cancer as these tumors are highly resistant to chemotherapy. Targeted drug delivery, usin

  4. Phallic and seminal masculinity: a theoretical and clinical confusion.

    Science.gov (United States)

    Figlio, Karl

    2010-02-01

    Both inside and outside psychoanalysis, the word, 'seminal', is used to praise a creative contribution to science and culture. Rarely, however, does it refer to male procreativity, to the structures and functions that subserve it or to the anxiety related to a threat to it. This situation becomes evident in the concept of castration anxiety, which typically refers, with Freud, to cutting off the penis and not to extirpating the testicles. This phallic theory has been debated, repudiated and ignored. While there is an alternative literature on non-phallic masculinity, it is scattered and rarely refers to seminal function. Freud's theory meets his requirement for a well-articulated representation of absolute loss as an experience, but this clear structure--and its repudiation--obscure the observation and theory of the internal world of the male. I propose the concepts of 'seminal masculinity' and 'seminal castration', which I ground in Melanie Klein's concept of depressive anxiety. I contrast them with phallic masculinity and phallic castration anxiety, which I ground in her concept of paranoid-schizoid anxiety. I argue that they meet Freud's requirement that castration be a potential experience and that understanding masculinity demands such a basis. PMID:20433478

  5. The Role of FSH in Prostate Cancer: A Case Report

    OpenAIRE

    Salvatore Catarinicchia; E David Crawford

    2016-01-01

    Castrate Resistant Prostate Cancer (CRPC) is a difficult entity to treat in the spectrum of prostate cancer disease. Recently, Follicle Stimulating Hormone (FSH) has been shown to play an important part in the natural history of prostate cancer disease progression (Crawford et al., 2014). Here, we discuss a now deceased 94 year-old patient who illustrates the importance of this.

  6. Growth performance, carcass and non-carcass characteristics of Mubende and Mubende×Boer crossbred goats under different feeding regimes

    DEFF Research Database (Denmark)

    Asizua, D.; Mpairwe, D.; Kabi, F.;

    2014-01-01

    evaluated the effects of supplementing grazing Mubende goats and their crossbreds (Mubende×Boer) with concentrates on growth, carcass and non-carcass characteristics. A 2×3 factorial treatment arrangement was used to randomly allocate 96 pure Mubende and Mubende×Boer castrates (mean±SE; 31.3±2.2 kg initial...

  7. Sex-specific effects of a parasite evolving in a female-biased host population

    Directory of Open Access Journals (Sweden)

    Duneau David

    2012-12-01

    Full Text Available Abstract Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration, which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  8. Pelleting of diet ingredients: Diet selection and performance in choice-fed growing pigs

    NARCIS (Netherlands)

    Brand, van den H.; Verstegen, M.W.A.; Poel, van der A.F.B.

    2007-01-01

    An experiment was completed with individually housed growing pigs to examine whether pigs can compose their optimal diet when allowed a choice of three different pellets. Forty cross-bred pigs (20 castrates and 20 gilts) with an initial live weight of 22.0 ± 2.1 kg were allocated to either a complet

  9. 76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

    Science.gov (United States)

    2011-04-05

    ... application (NADA) filed by Novartis Animal Health US, Inc. The NADA provides for the veterinary prescription... Ave., suite 300, Greensboro, NC 27408, filed NADA 141-320 that provides for the veterinary... associated with orthopedic surgery, ovariohysterectomy, and castration. The NADA is approved as of March...

  10. Diagnosis of chronic active hepatitis in a miniature schnauzer

    OpenAIRE

    Hendrix, Alana D.

    2004-01-01

    A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described.

  11. Efficacy of c-Met inhibitor for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Christensen James G

    2010-10-01

    Full Text Available Abstract Background Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC. Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. Methods We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. Results We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. Conclusions The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

  12. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: Results from the STAMPEDE and CHAARTED trials

    NARCIS (Netherlands)

    R.J. van Soest (Robert Jan); R. de Wit (Ronald)

    2015-01-01

    textabstractAndrogen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), fol

  13. Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations.

    Science.gov (United States)

    De Maeseneer, Daan Joost; Van Praet, Charles; Lumen, Nicolaas; Rottey, Sylvie

    2015-07-01

    Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing. PMID:25708954

  14. Quand Dulaurens publiait à Liège ses « obscénités »

    OpenAIRE

    Droixhe, Daniel

    2008-01-01

    Which role does sexuality play in the Chandelle d'Arras? The burlesque treatment of the Holy Virgin cult in Arras opens door to the personal fears of the author (castration, impotence) thru, thru a metaphorical travel to Paradise. The contest of the Old Regime morality and oppression is expressed by the drunken and Shakespearien street-singers, "vox populi".

  15. Sedation and dissociative anaesthesia in the horse

    OpenAIRE

    Marntell, Stina

    2004-01-01

    The overall aim of this investigation was to study the effects of different drug combinations for premedication and dissociative anaesthesia, to examine their suitability for field conditions and their ability to maintain cardiorespiratory function and provide sufficient analgesia for common, but challenging procedures such as castration. Haemodynamic parameters, pulmonary ventilation-perfusion relationships, and clinical effects were studied during sedation and dissociative anaesthesia. The ...

  16. I am Joaquin. Yo Soy Joaquin. An Epic Poem with a Chronology of People and Events in Mexican and Mexican American History.

    Science.gov (United States)

    Gonzales, Rodolfo

    Both Spanish and English versions of the epic poem "I Am Joaquin" are given in this book. "I Am Joaquin" is the first work of poetry to be published by Chicanos for Chicanos. It is a historical essay of the greatness and weakness of the Chicano people. Their psychological wounds, cultural genocide, social castration, nobility, courage,…

  17. The use of alfaxalone and remifentanil total intravenous anesthesia in a dog undergoing a craniectomy for tumor resection.

    Science.gov (United States)

    Warne, Leon N; Beths, Thierry; Fogal, Sandra; Bauquier, Sébastien H

    2014-11-01

    A 7-year-old castrated border collie dog was anesthetised for surgical resection of a hippocampal mass. Anesthesia was maintained using a previously unreported TIVA protocol for craniectomy consisting of alfaxalone and remifentanil. Recovery was uneventful, and the patient was discharged from hospital. We describe the anesthetic management of this case. PMID:25392553

  18. Correlations of visual scores, carcass traits, feed efficiency and retail product yield in Nellore cattle

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Cancian

    2014-02-01

    Full Text Available The growing use of visual scores (VS and ultrasound (US for carcass evaluation in breeding programs, calls for a knowledge of the relationships between these traits and other relevant characteristics, such as feed efficiency and production of commercial cuts. The objective of this study was to evaluate correlations between body visual scores and carcass traits identified by ultrasound (US and feed efficiency (FE, carcass weight (HCW, dressing percentage (DP and retail product yield (RPY in beef cattle. Nellore cattle (male, 42 non-castrated [NCAST] and 44 castrated [CAST] were evaluated by both VS and US, at the postweaning (15-month old and finishing phases (21-month old. Visual scores of conformation (C, precocity (P and muscling (M were assessed and the backfat thickness (UBFT, rump fat thickness (URFT and ribeye area (UREA were measured by ultrasound. Gain-to-feed (G:F ratio and residual feed intake (RFI were measured in feedlot. Hot carcass weight, DP and RPY were determined at harvest. Non-castrated cattle had greater HCW and RPY but lower UBFT and URFT than CAST. Postweaning VS and US were poorly correlated with FE in both sexual conditions. Finishing VS were negatively correlated with G:F in CAST and finishing URFT was negatively correlated with RPY in NCAST. The relationship of VS and US with feed efficiency and meat yield is affected by age at the date of evaluation and by castration. Feed efficiency is not related to the yield of meat cuts in Nellore cattle

  19. Successful treatment of mitral valve endocarditis in a dog associated with 'Actinomyces canis-like' infection.

    Science.gov (United States)

    Balakrishnan, N; Alexander, K; Keene, B; Kolluru, S; Fauls, M L; Rawdon, I; Breitschwerdt, E B

    2016-09-01

    Infective endocarditis, an inflammation of the endocardial surface due to invasion by an infectious agent, is more common in middle sized to large breed dogs. We herein report a case of mitral valve endocarditis in a 9-year-old male-castrated Weimaraner caused by an Actinomyces canis-like bacterium, not previously reported in association with infection in dogs. PMID:27364088

  20. Castrati singers: surgery for religion and art.

    Science.gov (United States)

    Koutsiaris, Epameinondas A; Alamanis, Christos; Eftychiadis, Aristotle; Zervas, Anastasios

    2014-01-01

    The act of castration was practiced from ancient times. In countries of Middle and Far East, castration was often done to provide eunuchs as guardians of the harems. In Europe and especially in Italy, it was carried out to preserve the male voice unbroken into adult life. From 16th century till the end of 18th century, castrati singers dominated opera with their supernatural voices. Boys were castrated mainly before the age of 9 years and when they grew up they had feminine characteristics, such as smooth, hairless bodies, breasts, infantile penis. The training procedure to become a castrato singer was very intense and lasted up to ten years. The most common surgical technique was either to sever the spermatic cords or crush the testis with the fingers. The voice of a castrato was the outcome of a larynx the size of a child's combined with the lung volume of an adult male. The castrati singers became superstars who dominated opera, singing both male and female roles for more than 200 years. Castrated for art, the beauty, range and flexibility of their voices raised them to mythical status. PMID:25665280