WorldWideScience

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. Castration anxiety and phobias.

    Science.gov (United States)

    Cogan, Rosemary; Larrabee, Linda K; Wyatt, Ian M; Ontiberoz, Amanda; Waters, Stephanie K; Werner, Mitzi L; Miller, Andrea L; Lovelady, Adrianne C; Hurt, Tilmon J; Hardin, Edward D; Gonzalez, Patricia M

    2002-12-01

    Based on Freud's case study of "Little Hans," the authors tested the hypothesis that men with phobias would score higher on castration anxiety than men without phobias. College men with either average or high scores on the Fears Scale of the MMPI-2 (n = 10 men in each group) responded to the Thematic Apperception Test, which was scored for castration anxiety. Men with high scores on the Fears Scale had higher scores on castration anxiety than men with average scores on the Fears Scale. The findings are consistent with Freud's hypothesis about phobias. PMID:12585544

  3. 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...... underlines that they may be detained ‘indefinitely’. And the response report of the European Committee for the Prevention of Torture and Inhumane or Degrading Treatment or Punishment (CPT) to the Czech Government also emphasises—as part of the Czech Criminal Code—the possibility of ‘security detention’ that...

  4. [Self-castration with suicide].

    Science.gov (United States)

    Keil, W; Betz, P; Penning, R

    1994-01-01

    Suicide of a 31 year old man with multiple slashes and stab wounds including complete amputation of penis, scrotum and testicles is reported. Wound patterns in genital self-mutilations are discussed. Despite serious loss of blood the reported survival periods are remarkable; death from bleeding seems to be rare. A review of similar cases shows that self-castrations as well as other self-inflicted genital mutilations are usually associated with psychiatric disorders and transsexuality or hypersexuality. PMID:7979869

  5. Pedophilia: analysis against pedophilic chemical castration

    OpenAIRE

    Karla Ferraz dos Anjos, Vanessa Cruz Santos

    2009-01-01

    Objectives: to describe about the main reasons of being against pedophilic’s castration. Methodology: review literature study by collecting data from the National Library of Medicine (PUBMed), through internet, at the website of the Biblioteca Virtual em Saúde (BVS), using the followings describers: pedophilia, disorder, castration, treatment. Results: based on the fact that pedophilia doesn’t depend on sexual act to be marked, and it is classified as a personality disorder and a sexual adult...

  6. Acute Cold / Restraint Stress in Castrated Rats

    Directory of Open Access Journals (Sweden)

    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.

  7. Body measurements and carcass traits of castrated and non-castrated Mediterranean buffalos

    Directory of Open Access Journals (Sweden)

    Renata de Oliveira Santos Ramalho

    2013-01-01

    Full Text Available In this study was evaluated the effect of sex condition on body measurements and carcass traits as well as the correlations between them, using data of 20 Mediterranean, from Fazenda Três Rios, at Casimiro de Abreu, Rio de Janeiro, managed in tangola grass pasture, receiving mineral salt ad libitum, slaughtered at approximately 462,05 kg (±28.34. The body measurements were: thoracic depth (TD, croup length (CL, withers height (WH, rump width (RW, rump height (RH, ischium distance (ID, cushion thickness (CT, thoracic perimeter (TP, and dorsal line length (DLL. Data were submited to variance analysis and Pearson correlation. The castrated animals presented higher height of croup. Non-castrated animals had bigger yield from leather than the castrated animals, which influenced the lowest yield of carcass regarding the castrated ones. There was no difference for yield of paws, innards and head in function of the sexual condition. There was significant correlation between the slaughter weight (SW and the following corporal measures: TP, TD, RW, ID and WH.

  8. 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

  9. [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

  10. 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

  11. HUMAN RIGHTS AND PROSPECTS FOR APPLYING CHEMICAL CASTRATION IN RUSSIA

    OpenAIRE

    Suzanna Karoevna ABRAMYAN; Arseny Igorevich ZAITSEV; Igor Stanislavovich DMITRIYEV

    2015-01-01

    I The paper examined challenges related to applying chemical castration the Russian community has faced, and assessed the prospect for further implementation as well. The issue has triggered an ample debate in various circles as a new probable way to prevent sexual crime events. The authors inferred that chemical castration should be an option of a complex of measures for pre-venting relapse into pedophilia.

  12. Castration of a Black Rhinoceros Diceros Bicornis Minor

    Directory of Open Access Journals (Sweden)

    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.

  13. HUMAN RIGHTS AND PROSPECTS FOR APPLYING CHEMICAL CASTRATION IN RUSSIA

    Directory of Open Access Journals (Sweden)

    Suzanna Karoevna ABRAMYAN

    2015-02-01

    Full Text Available I The paper examined challenges related to applying chemical castration the Russian community has faced, and assessed the prospect for further implementation as well. The issue has triggered an ample debate in various circles as a new probable way to prevent sexual crime events. The authors inferred that chemical castration should be an option of a complex of measures for pre-venting relapse into pedophilia.

  14. THE THREE MEANS TO NEGATE CASTRATION

    Directory of Open Access Journals (Sweden)

    Francisco Ramos de Farias

    2010-12-01

    Full Text Available When crossing from the natural state to the cultural state, the human breed, in response to the absence captured in the body of the woman, disposes of three means to negate castration. They are three defensive means used by the subject to avoid being totally reduced to the condition of a simple object of desire of the Other. In dealing with repression, we have the psychic inscription “there is no penis” in the body of the woman substituted by “I do not know”, which drives the subject to glide through culture in search of objects directed to a type of knowledge imprinted by paternal anteriority. Concerning disavowal, we simultaneously have the negation and the affirmation of the existence of a penis in the body of a woman by means of the two coexisting psychical chains that do not contradict each other and hold the fetish as the paradigm. Finally, in foreclosure, the absence in the body of a woman is not captured, placing the subject in the position of being the phallus of the mother.

  15. 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.

  16. 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

  17. Castration increases elimination of perfluorooctanoic acid (PFOA) in male rats

    International Nuclear Information System (INIS)

    There is a marked sex difference in whole body elimination of PFOA in rats with females (t1/2) 1/2 = 15 days). The authors were interested in determining if the levels of circulating androgens or estrogens modulate PFOA elimination. That is, if castrated males pretreated with estradiol exhibit a female pattern of PFOA elimination and if ovariectomized females pretreated with testosterone exhibit the male pattern. Castration of males greatly increased the elimination of [1-14C]PFOA (9.4 μmol/kg, ip) into both urine and feces, but castration plus estradiol produced no further augmentation. In female rats, neither ovariectomy nor ovariectomy plus testosterone affected the elimination of PFOA. They conclude that a factor produced by the testis, most likely androgens, modulate the elimination of PFOA in the male rat

  18. 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...

  19. 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

  20. 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

  1. 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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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...

  6. 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. PMID:26428645

  7. 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...

  8. 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 ...

  9. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice.

    Science.gov (United States)

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  10. Stress responses in lambs castrated with three different methods

    Directory of Open Access Journals (Sweden)

    Paola Sandra Nicolussi

    2010-01-01

    Full Text Available The present work was conducted to evaluate the animal response to stress in lambs caused by three different castration techniques. Forty-six male lambs aged 4-5 months were randomly allocated to one of four groups including Burdizzo (B, scrotal ablation (SA, orchiectomy (OR and control handling (H. Local anaesthesia (lidocaine 2% was administered in both spermatic cords and the scrotal neck of lambs before each treatment. Blood samples were collected at -30, -10, +1, +20, +40, +60, +120, and +180 minutes. Serum cortisol concentrations were determined using a competitive immunoassay and the area under the curve (AUC was calculated for each lamb. The following biochemical parameters were assayed for each animal at each time point: alanine aminotransferase (ALT, aspartate aminotransferase (AST, lactate dehydrogenase (LDH, creatine kinase (CK and glucose (GLU. The time needed for total lesion resolution and weight gain of each animal was recorded. Orchiectomy elicits the greatest cortisol response, significantly greater than that seen in similarly handled controls (P≤0.01, Burdizzo and scrotal ablation groups (P≤0.05. The serum cortisol AUC was higher in the scrotal ablation group (P≤0.05 than controls, but lower than in the orchiectomy group (P≤0.05. The Burdizzo group didn’t differ from controls. Serum glucose levels of the castrated lambs differed significantly from the control group, following a trend similar to cortisol. No change was seen in ALT, AST, LDH or CK. No difference in weight gain was seen among the groups. Our results suggest that use of the Burdizzo is the preferable castration technique for adult lambs, while scrotal ablation is a valid surgical alternative to orchiectomy and permits more rapid wound healing that is ideal for extensive management where flocks are not under close observation.

  11. Castration resistant prostate cancer - something new in the year 2014?

    International Nuclear Information System (INIS)

    Prostate cancer (PC) is the most frequent solid neoplasm in Europe and therefore is regarded as one of the major medical problem of the male population. PC is extremely complicated and interindividual different tumor. The method of treatment depends on several factors, but mainly on the stage of prostate cancer. The term Hormone resistant (refractory) prostate cancer (HRPC) was used in older terminology. HRPC is cancer that progresses despite castrate levels of testosterone achieved androgen deprivation therapy (ADT), which is resistant to any hormonal therapy. Currently is increasingly used (instead of name HRPC) name CRPC – so called PC resistant for castration (CRPC – castration resistant prostate cancer), which is still able to respond to certain hormonal manipulation, although it meets the the criteria for HRPC. This state probably arises from either clonal selection of androgen – independent cell lines or increased ligand – independent activation of androgen receptors. Men with CRPC are quite a heterogeneous group; they include men with increasing prostate specific antigen (PSA) only and no demonstrable metastases, and men who have many bone and/ or visceral metastases, pain and poor functional status. Survival can range from only a few months to 4 years or more. Historically, therapy had little effect beyond modest palliation. More recently, significantly more options have become available and there are now several treatments that not only improve quality of life and pain palliation, but also increase overall survival. Some of the trials with important results for the treatment of CRPC are summarized in this paper. Objectives of article: provide information to the general medical community (and especially urologists and oncologists) about the possible pathogenesis of CRPC, complicated issues of treatment and evaluation of its effectiveness in patients with CRPC. The article presented basic data on the current and future possibilities of such therapy

  12. Castration of sex offenders: prisoners' rights versus public safety.

    Science.gov (United States)

    Scott, Charles L; Holmberg, Trent

    2003-01-01

    Sexual victimization of children and adults is a significant treatment and public policy problem in the United States. To address increasing concerns regarding sex offender recidivism, nine states have passed legislation since 1996 authorizing the use of either chemical or physical castration. In most statutes, a repeat offender's eligibility for probation or parole is linked to acceptance of mandated hormonal therapy. Future legal challenges to this wave of legislation will probably include arguments that such laws violate constitutional rights guaranteed to the offender by the First, Eighth, and Fourteenth Amendments. When the promise of freedom is predicated on mandated treatment, the clinician must carefully assess the validity of informed consent. PMID:14974806

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. [Current status of castration-resistant prostate cancer translational research].

    Science.gov (United States)

    Maeno, Atsushi; Habuchi, Tomonori

    2016-01-01

    Recently, new drugs including abiraterone and enzalutamide have been able to be used for castration resistant prostate cancer(CRPC) patients. However, a subset of these patients who receive the new drugs does not response to the therapies. Furthermore, most patients who initially response to the drugs, progress to secondary resistance eventually. Therefore, it is important to investigate a novel therapeutic target and a novel treatment-selection marker for CRPC. In this review, we focused on AR-V7, TMPRSS2-ERG fusion gene and EP4 antagonist as representative translational researches. PMID:26793877

  16. Gender Preference in the Sexual Attractions, Fantasies, and Relationships of Voluntarily Castrated Men

    Science.gov (United States)

    Handy, Ariel B.; Jackowich, Robyn A.; Wibowo, Erik; Johnson, Thomas Wayne; Wassersug, Richard J.

    2016-01-01

    Introduction Some men seek castration outside a clear medical need. This study explored how their sexuality changed after castration. Aim To explore changes in preferred gender(s) of sexual attraction, fantasy, and relationships in voluntarily castrated men with or without gonadal hormone therapy. Methods A questionnaire was posted at http://www.eunuch.org that yielded data on men who had been voluntarily castrated physically (n = 198) or chemically (n = 96). Main Outcome Measures Respondents were asked to report retrospectively on their sexuality, including their sexual activity and which gender(s) they were sexually attracted to, fantasized about, or had sexual relations with 6 months to 1 year before and after castration. Results A substantial proportion of men remained sexually active after castration; 37% had sex at least several times per week. Most respondents did not report a change in preferred gender(s) of attraction (65%, n = 181), fantasies (62%, n = 169), or sexual relationships (66%, n = 163), although approximately 20% to 30% of respondents did report such changes and 8% to 11% became non-sexual after castration. Respondents who were attracted to and fantasized about “only men” or who had sexual relationship with “only women” before castration were the least likely to report a change subsequent to castration. Respondents who were taking neither supplemental testosterone nor estrogen were more likely to report (i) becoming attracted to no one, (ii) fantasizing about no one, and (iii) becoming sexually inactive. Conclusion Sexual changes in voluntarily castrated men vary and can be influenced by various factors including the use of supplemental testosterone or estrogen therapy. PMID:26944778

  17. 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

    2016-01-01

    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 (p<0.05). Compared with entire males, the castrates had lower pH and shear force values (p<0.05). However, castrates had higher L*, a*, and b* values compared with entires (p<0.05). An analysis of the fatty acid profile revealed that the muscles of entire and castrate elk had the most abundant concentrations of the following fatty acids: palmitic acid (C16:0) of the saturated fatty acid, and oleic acid (C18:1n-9) of the unsaturated fatty acid. The entire elk contains higher proportions of linoleic acid (C18:3n6), eicosenoic acid (C20:1n9), and arachidonic acid (C20:4n6) (p<0.05). Cholesterol content in elk was not affected by castration. The predominant free amino acid was glutamic acid related to umami 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

  18. Src controls castration recurrence of CWR22 prostate cancer xenografts

    International Nuclear Information System (INIS)

    Recurrence of prostate cancer (CaP) after androgen-deprivation therapy continues to have the greatest impact on patient survival. Castration-recurrent (CR)-CaP is likely driven by the activation of androgen receptor (AR) through multiple mechanisms including induction of AR coregulators, AR mutants or splice variants, and AR posttranslational modification such as phosphorylation by Src-family and Ack1 tyrosine kinases. Here, we address whether Src is required for the CR growth of human CWR22 CaP xenografts. The shRNA-mediated Src knockdown or treatment with the Src inhibitors, dasatinib or KXO1, reduced CaP recurrence over controls and increased time-to-recurrence following castration. Moreover, CR-CaP [Src-shRNA] tumors that recurred had similar Src protein and activation levels as those of parental cells, strengthening the notion that Src activity is required for progression to CR-CaP. In contrast, the ability of dasatinib or KXO1 to inhibit Src kinase activity in vitro did not correlate with their ability to inhibit serum-driven in vitro proliferation of CR and androgen-dependent stable cell lines derived from CWR22 tumors (CWR22Rv1 and CWR22PC, respectively), suggesting that the in vitro proliferation of these CaP lines is Src independent. Taken together, these findings strongly suggest that Src is a potent and specific therapeutic target for CR-CaP progression

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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. PMID:26776048

  2. Depression of nocturnal pineal serotonin N-acetyltransferase activity in castrate male rats

    International Nuclear Information System (INIS)

    Pineal serotonin N-acetyltransferase (NAT) activity was examined in intact rats, castrated rats, and in rats that had been castrated and had received testosterone proprionate. Castration resulted in significantly depressing nocturnal levels of pineal NAT (p<0.05) when compared to enzyme activity in intact rats. Testosterone proprionate administration restored plasma LH levels to normal values in castrate rats but did not induce nocturnal pineal enzyme activity to levels seen in the pineal glands of intact rats. The data substantiate the existence of a feedback control of pineal biosynthetic activity by the hypophyseal-gonadal system, but the identity of the hormone(s) responsible for regulation of pineal NAT activity is not known. (author)

  3. 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...

  4. The unfolding treatment landscape for men with castration-resistant prostate cancer

    OpenAIRE

    Kim, Jenny J.; Keizman, Daniel; Denmeade, Samuel R.; Antonarakis, Emmanuel S.

    2011-01-01

    Castration-resistant prostate cancer (CRPC) is a fatal disease in virtually all patients. Docetaxel chemotherapy became the standard front-line agent based on the results of the TAX327 trial in 2004, with a survival advantage of 3 months achieved over mitoxantrone. Over the past few years, an improved understanding of the molecular biology of castration-resistance has resulted in expansion of the treatment armamentarium for advanced prostate cancer with the emergence of novel androgen recepto...

  5. Preoperative ketoprofen administration to piglets undergoing castration does not affect subsequent growth performance

    OpenAIRE

    Cassar, Glen; Amezcua, Rocio; Tenbergen, Ryan; Friendship, Robert M.

    2014-01-01

    The purpose of this study was to determine if treatment of pigs with ketoprofen (3 mg/kg body weight) before castration at 7 days of age would affect subsequent growth during the suckling period. Piglets from 301 litters were treated with ketoprofen or a placebo and weighed at castration and at weaning. There was no difference in growth rate between the 2 groups of pigs.

  6. 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.

  7. 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.

  8. 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.

  9. [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

  10. 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.

  11. 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.

  12. 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.

  13. 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

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

    Science.gov (United States)

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

    2012-07-12

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

  15. 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

    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 that...... survive from which regeneration occurs on testosterone replacement....

  16. 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...

  17. Ham and belly processing characteristics of immunological castrated barrows (Improvest) fed ractopamine hydrochloride (Paylean).

    Science.gov (United States)

    Lowe, B K; Overholt, M F; Gerlemann, G D; Carr, S N; Rincker, P J; Schroeder, A L; Petry, D B; McKeith, F K; Allee, G L; Dilger, A C

    2016-02-01

    Effects of sex class (physically castrated, PC or immunologically castrated, IC) and diet (0 or 5mg/kg ractopamine hydrochloride, RAC) on characteristics of ham and bellies were determined from pigs slaughtered in three groups with similar ending live weights. One carcass per pen per marketing group (n=8) was selected to evaluate further processing characteristics. Data were analyzed as a 2×2 factorial design with a split plot in time and fixed effects of sex, diet, marketing group, and their interactions. IC fresh bellies were thinner (P0.05) fresh ham or belly characteristics but decreased (P<0.01) fat in cured PC bellies. Marketing group affected (P<0.05) fresh quality, processing characteristics, and composition of hams and bellies. Immunological castration and RAC produced leaner finished products but did not alter processing yield of hams or bacon. PMID:26584399

  18. Modified-closed castration: a novel technique for sea otter (Enhydra lutris nereis) orchiectomies.

    Science.gov (United States)

    McDermott, Alexa J; Clauss, Tonya; Sakals, Sherisse; Mejia, Johanna; Radlinsky, MaryAnn G

    2013-09-01

    A novel surgical technique was used in the routine castrations of two intact male southern sea otters, Enhydra lutris nereis, housed at the Georgia Aquarium (Atlanta, Georgia, USA). This technique involved incising the parietal vaginal tunic to allow placement of double ligation of the ductus deferens, testicular artery, and pampiniform plexus en masse. After ligating and transecting these structures, they were introduced back into the tunic, which was closed with a circumferential ligature. The incision site was closed in a routine manner. Both otters recovered well from the procedure. One otter had mild cutaneous dehiscence postoperatively, and the other had no obvious complications. Benefits of this procedure include reduced risk of ligature slippage or loosening and resultant hemorrhage, as provided by the traditional open portion of the castration, and decreased postoperative swelling, as provided by the closed part of the castration. To the authors' knowledge, this is the first time this technique has been described for use in sea otters. PMID:24063115

  19. 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

  20. 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...

  1. 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...

  2. 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

    The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8) for a...... females). Total hip Z-scores were castration patients and 13% of bicalutamide patients. In 38% of patients, 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 with...

  3. 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,...

  4. 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.

  5. Developing imaging strategies for castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for 'radiographic' progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na18F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as 18F-FDHT and 89Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to

  6. 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...

  7. The impact of surgical castration on sexual recidivism risk among sexually violent predatory offenders.

    Science.gov (United States)

    Weinberger, Linda E; Sreenivasan, Shoba; Garrick, Thomas; Osran, Hadley

    2005-01-01

    The relationship of surgical castration to sexual recidivism in a sexually violent predator/sexually dangerous person (SVP/SDP) population is reviewed. A review of the literature on castrated sex offenders reveals a very low incidence of sexual recidivism. The low sexual recidivism rates reported are critiqued in light of the methodologic limitations of the studies. Better designed testicular/prostate cancer studies have demonstrated that, while sexual desire is reduced by orchiectomy, the capacity to develop an erection in response to sexually stimulating material is not eliminated. The relevance of this literature to SVP/SDP commitment decisions and ethics is discussed. Two vignettes of castrated, high-risk sex offenders illustrate how to address risk reduction. Two tables are presented: the first outlines individual case data from a difficult-to-obtain report, and the second summarizes the most frequently cited castration studies on sexual recidivism. Orchiectomy may have a role in risk assessments; however, other variables should be considered, particularly as the effects can be reversed by replacement testosterone. PMID:15809235

  8. 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.

  9. 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.

  10. Color stability and sensory characteristics of fresh and enhanced pork loins from immunologically castrated barrows.

    Science.gov (United States)

    Jones-Hamlow, K A; Tavárez, M A; Boler, D D; Schroeder, A L; Prusa, K J; Dilger, A C

    2015-02-01

    Our objective was to evaluate color changes during storage of fresh pork chops and enhanced and nonenhanced loin quality from anti-gonadotropin-releasing factor (Improvest) immunologically castrated (IC) barrows. In study 1, treatments evaluated were IC barrows, IC barrows fed ractopamine (IC+RAC), physically castrated (PC) barrows, intact males (IM), and gilts. Fresh loins were evaluated for sensory characteristics and instrumental tenderness including both Warner-Bratzler Shear force (WBSF) and star probe force. In study 2, treatments evaluated were IC barrows fed 0.55% and 0.65% standard ileal digestible (SID) lysine and PC barrows fed 0.55% SID lysine. Loin chops were displayed for 7 d, and color was evaluated. The remaining loin was halved, and one half was enhanced with a 3.5% salt and phosphate solution. Enhanced loins were evaluated for sensory characteristics and instrumental tenderness. In both studies, pen served as the experimental unit for all traits measured. Data from individual animals were averaged by pen and analyzed, per study, as a 1-way ANOVA using the MIXED procedure of SAS. In study 1, there were no differences ( 0.05) between treatments for juiciness, tenderness, chewiness, or off-flavor. Intact males had the most intense ( 0.05) boar aroma. Gilts had the most intense ( 0.05), and there were no interactions of enhancement with castration treatments. These data suggest that immunological castration does not negatively impact the color stability, sensory characteristics, or tenderness of enhanced or nonenhanced pork loins. PMID:26020759

  11. 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 ...

  12. 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)

  13. 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

  14. 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...

  15. State-Of-The-Art Treatment in Castration-Resistant Prostate Cancer

    OpenAIRE

    Elena Castro; Nuria Romero; David Olmos

    2014-01-01

    Prostate cancer (PrCa) is the most common cancer type in men in developed countries. In the last few years, a dramatic change has occurred in the understanding of castration-resistant PrCa which has led to the development of new drugs that have an impact on patient survival. This review summarises the recent advances in the management of the disease.

  16. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern; Høyer, Morten; Jensen, Niels Viggo; Saxe, Charlotte; Sengeloev, Lisa

    2010-01-01

    DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC......), adequate function of liver, kidney and bone marrow; ECOG performance status...

  17. 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.

  18. 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

  19. 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)

  20. Parasitic castration: a perspective from a model of dynamic energy budgets.

    Science.gov (United States)

    Hall, Spencer R; Becker, Claes; Cáceres, Carla E

    2007-08-01

    Models of the evolution of virulence have typically focused on increased mortality, one of two negative effects that parasites can inflict on their host. Those that consider the other effect, fecundity reduction, can predict that parasites should completely sterilize their hosts. Although this prediction seems extreme, sterilization features prominently in a fascinating strategy, parasitic castration. Such castration can be accompanied by gigantism (unusually large growth of infected hosts), long infectious periods, and fecundity compensation (where, before heavy parasite burdens ensue, newly infected hosts reproduce earlier/more than they would if not infected). Using a model of dynamic energy budgets (DEB), we show how these results readily emerge, assuming that parasites consume energy reserves of the host. The simple, but mechanistic, DEB model follows energy flow though hosts and parasites, starting with ingestion, and continuing with storage of assimilated energy, and use of those reserves for growth and reproduction, as allocated by the host according to the "κ-rule". Using this model, we compare and contrast two strategies for parasites. "Consumers" only steal energy from their hosts, thereby indirectly altering allocation of energy to growth and reproduction, reducing fecundity, and enhancing mortality. "Castrators" steal energy but also directly modify the scheme by which hosts allocate reserve energy, shunting resources from reproduction to growth. Not surprisingly, the model predicts that this strategy should promote gigantism, but it also forecasts longer infectious periods and fecundity compensation. Thus, commonly observed characteristics of parasitic castration readily emerge from a mechanistic model of energy flow using a minimal number of assumptions. Finally, the DEB model for both "consumers" and "castrators" highlight that variation in resources supplied to hosts promotes variation in virulence in a given host-parasite system, holding all else

  1. 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

  2. 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...

  3. 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 ...

  4. Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue

    OpenAIRE

    Jiao, Qianning; Pruznak, Anne M.; Huber, Danuta; Vary, Thomas C; Lang, Charles H.

    2009-01-01

    Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which...

  5. 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

    investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). INTERPRETATION: No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with......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 final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early...

  6. 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...

  7. 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...

  8. 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

  9. 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...

  10. 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...

  11. 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...

  12. Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer

    OpenAIRE

    Lin, H-M.; Castillo, L.; Mahon, K L; Chiam, K; Lee, B Y; Nguyen, Q.; Boyer, M. J.; Stockler, M R; Pavlakis, N; Marx, G.; Mallesara, G; Gurney, H; Clark, S J; Swarbrick, A; Daly, R. J.

    2014-01-01

    Background: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. Methods: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate c...

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

    OpenAIRE

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

    2011-01-01

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

  14. 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......-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel....

  15. 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

  16. Partner preference behavior of estrous female rats affected by castration of tethered male incentives.

    Science.gov (United States)

    Broekman, M; de Bruin, M; Smeenk, J; Slob, A K; van der Schoot, P

    1988-09-01

    Estrous female rats were allowed to interact with either of two tethered intact male rats or to stay in an empty middle part of a three-compartment observation cage during a 60-min test. Sexual interactions occurred with both males (resulting in one to five ejaculations) but most time was spent in the empty compartment. After castration of one of the males, females spent more time with this male than with the intact male, although sexual interactions continued with both incentive animals. This "preference" for the castrated male persisted through the second hour of observation in a second experiment (total test time 115 min) although sexual interactions had virtually ceased during this period. Females' preference for castrated males seemed largely the consequence of aversion to genital stimulation received during intromissions by intact animals: (a) when intromissions were prevented through vaginal occlusion, intact males became by far the preferred partners for the whole 2-hr period of testing while sexual behavior continued to occur throughout the test; (b) when choice was allowed between a testosterone-treated ovariectomized female and an intact male, sexual interaction occurred with both tethered incentive rats but the female became the preferred animal. The results suggest that two opposite tendencies play a role in sexual motivation of estrous female rats: attraction resulting from the action of ovarian hormones on the central nervous system and rejection resulting from genital sensory stimulation through the male's genitalia. PMID:3169698

  17. 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.

  18. Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

    Directory of Open Access Journals (Sweden)

    Afif Rieth Nery-Aguiar

    2016-02-01

    Full Text Available OBJECTIVES: Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20 and group II (tamoxifen, n=20, receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student’s t tests (p<0.05. RESULTS: The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001. CONCLUSIONS: According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Growth performance of immunologically castrated (with Improvest) barrows (with or without ractopamine) compared to gilt, physically castrated barrow, and intact male pigs.

    Science.gov (United States)

    Puls, C L; Rojo, A; Ellis, M; Boler, D D; McKeith, F K; Killefer, J; Gaines, A M; Matzat, P D; Schroeder, A L

    2014-05-01

    The study used a randomized complete block design (blocking factor was date of start on test) with 5 treatments: 1) physically castrated barrows (PC), 2) intact males (IM), 3) gilts (G), 4) immunologically castrated barrows (IC), and 5) immunologically castrated barrows fed ractopamine at 5 mg/kg (IC+RAC). The study used 192 pigs and was performed from the 16 wk of age (67.2 ± 2.52 kg BW) to a pen mean BW of 132.5 ± 3.60 kg. For IC+RAC, ractopamine was fed for the final 23 d of the study. Pigs were housed in groups of 4 (10 groups for PC, IM, G, and IC and 8 groups for IC+RAC) in a finishing building at a floor space of 1.18 m(2)/pig. Diets were formulated to meet requirements of IM except that the diet for the IC+RAC fed during the ractopamine feeding period was formulated to meet requirements of pigs on that treatment. Pigs had ad libitum access to feed and water throughout the study period and were individually weighed at the start, wk 2 and 4, and subsequently every week until the end of study. For the overall study period, IC had greater (P ≤ 0.05) ADG than the other genders (1,150, 1,024, 1,064, and 954 g/d for IC, PC, IM, and G, respectively; SEM = 25.8) and required fewer days to reach slaughter weight than the other genders (58.1, 61.6, 61.6, and 66.5 d for IC, PC, IM, and G, respectively; SEM = 1.26). Overall ADFI was less (P ≤ 0.05) for IM and G than IC and PC, which were similar (P > 0.05) in this respect (3.11, 3.06, 2.68, and 2.75 kg/d for IC, PC, IM, and G, respectively; SEM = 0.061). Overall G:F was greater (P ≤ 0.05) for IM than the other genders; IC had greater overall G:F than PC and G, which were similar in this respect (0.371, 0.335, 0.397, and 0.347 kg/kg for IC, PC, IM, and G, respectively; SEM = 0.0068). Immunologically castrated barrows had greater (P ≤ 0.05) ADG (30.7%) and ADFI (22.5%) than PC from the second week following the second Improvest dose to the end of the study. During the ractopamine feeding period, IC+RAC had

  4. 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...

  5. Update on options for treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2010-03-01

    Full Text Available Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC, the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16 in CRPC, several newer cytotoxic drugs (epothilones, satraplatin, targeted agents (abiraterone, MDV3100 and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cells

  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

    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.

  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. 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.

  10. Dominant-Negative Androgen Receptor Inhibition of Intracrine Androgen-Dependent Growth of Castration-Recurrent Prostate Cancer

    Science.gov (United States)

    Kantor, Boris; Li, Xiangping; Haack, Karin; Moore, Dominic T.; Wilson, Elizabeth M.

    2012-01-01

    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. PMID:22272301

  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. 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

  13. 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

  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. 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

  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. 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.

  19. AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation

    Science.gov (United States)

    Zhu, Shimiao; Shang, Zhiqun; Tian, Hao; Flores-Morales, Amilcar; Niu, Yuanjie

    2016-01-01

    The mechanism of neuroendocrine transdifferentiation (NED) during the development of castration-resistant prostate cancer (CRPC) remains undefined. Although androgen-deprivation therapy (ADT) can impair tumor cell growth, ADT can also triggers a parallel reaction, leading to increased neurotensin (NTS) production in cancer associated stromal cells which drives NED. Here, we systematically explore the NTS network in tumor microenvironment that drives NED following ADT. The CK8+/CK14+ intermediate cells, as opposed to other epithelial cells, can be transdifferentiated to neuroendocrine (NE) status by excessive NTS through simultaneous activation of neurotensin receptor 1 (NTSR1)-PRKACB and 3 (NTSR3)-AHNAK axes. The importance of PRKACB and AHNAK in NED development was then confirmed in human prostate tumor tissues. More importantly, we demonstrated SR48692 (an inhibitor of NTSR1) could inhibit NED and prevent castration resistance in prostate tumor from xenografts and TRAMP models. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of NTS following ADT.

  20. 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

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. [Longitudinal studies on gonadotropin levels in patients with Turner's syndrome and patients with prepubertal castration].

    Science.gov (United States)

    Maesaka, H; Tachibana, K; Suwa, S

    1984-05-20

    Basal and LH-RH induced plasma FSH and LH levels were determined longitudinally in 41 patients aged 4 to 22 years with Turner's syndrome and in 4 male patients with prepubertal castration. In 12 patients with Turner's syndrome over 18 yrs of age without pubertal change, basal and LH-RH induced FSH levels studied at age 11--22 yrs were all significantly increased over normal levels. However, some of these patients had normal basal and LH-RH induced LH levels. In 5 patients with mosaic Turner's syndrome with spontaneous puberty, basal and LH-RH induced FSH and LH levels studied at age 6--12 yrs were always within the normal range for age-matched controls. In 10 patients studied at age 11--18 yrs, basal and LH-RH induced FSH levels were also strikingly increased over normal levels except for one patient. This patient had normal basal FSH and LH levels and serum estradiol level was increased from 49 to 199 pg/ml after HMG test. In 14 patients aged 4--10 years, nine patients had elevated basal FSH levels and abnormally high responses to LH-RH. The remaining 5 patients had normal basal FSH levels, and 3 of them also had normal FSH responses to LH-RH. The data on the 5 patients studied again at the age of greater than 13 yrs rose to high levels in adult castrated ranges. In 24 patients aged 4 to 17 years, 23 patients were thought to have no ovarian function, and one was thought to have spontaneous puberty. In 4 male patients with prepubertal castration, basal and LH-RH induced FSH levels were increased over normal levels after 11 yrs of age. However, basal LH levels in some patients were within the normal range for age-matched controls after 12 yrs of age. From these results, we conclude that basal and LH-RH induced FSH levels may provide definitive evidence of absent ovaries or testes in patients over 11 yrs of age with primary hypogonadism. PMID:6436079

  6. 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

  7. 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.

  8. 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

  9. Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    V Noronha

    2014-01-01

    Full Text Available Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2, progression (1 and logistics (1. Two of the three patients with measurable disease attained a partial remission (PR. Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN, all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.

  10. Androgen receptor variant-7: an important predictive biomarker in castrate resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2015-06-01

    Full Text Available The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7, in circulating tumor cells (CTCs from metastatic castrate-resistant prostate cancer (mCRPC patients receiving enzalutamide or abiraterone. The findings were striking, none of the 18 patients with detectable AR-V7 in CTCs had prostate-specific antigen (PSA responses. Further, the median time to PSA progression after enzalutamide or abiraterone treatment was only 1.3-1.4 months in AR-V7-positive patients as compared to 5.3-6.1 months in AR-V7 negative patients. AR-V7 in CTCs was also associated with shorter survival.

  11. 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...

  12. 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

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

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    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

  14. Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

    Science.gov (United States)

    Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

    2015-10-01

    The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

  15. Variant allele of HSD3B1 increases progression to castration-resistant prostate cancer

    Science.gov (United States)

    Nastiuk, Kent L.; Li, Jinliang; Gu, Jun; Wu, Ming; Zhang, Qimin; Lin, Hanqing; Wu, Denglong

    2016-01-01

    BACKGROUND 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which is a rate-limiting enzyme that catalyzes the conversion of adrenal-derived steroid dehydroepiandrosterone to DHT, may be a promising target for treating castration-resistant prostate cancer (CRPC). METHODS From 2004 to 2011, a total of 103 consecutive patients presenting with advanced prostate cancer were included in this study. All patients were treated with surgical castration as androgen deprivation therapy (ADT). Germline DNA was extracted from archived tissue from each patient and sequenced. PSA half-time (representing rate to PSA nadir after ADT), the incidence of, and time to CRPC occurrence, and cause-specific mortality rates were determined during the 3-10 year follow-up. The perioperative data and postoperative outcomes are compared. The patients were retrospectively analyzed for survival time. RESULTS Of the 103 patient samples analyzed, 18 harbored a heterozygous variant (1245C) HSD3B1 gene, while 85 patients were homozygous wild-type (1245A) for HSD3B1. The two groups were homogenous for age, PSA, Gleason and metastases rate preoperatively. The incidence of CRPC observed in the variant group was significantly higher than that of wild-type group (100% vs 64.7%, respectively; p = 0.003). Despite this higher incidence of CRPC, there were no significant differences in time to develop CRPC, or in cause-specific mortality. Further, neither PSA half-time, nor time to biochemical recurrence (rising PSA is only one of the defining characteristics of CRPC) were different between the variant and wild-type groups. CONCLUSION Prostate cancer patients who harbored the heterozygous variant HSD3B1 (1245C) are more likely to develop to CRPC, but do not have shorter time to biochemical recurrence, shorter survival time or higher mortality risk. PMID:25731771

  16. Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer

    International Nuclear Information System (INIS)

    The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearch™. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole genome amplification (WGA) followed by gene copy number analysis via array comparative genomic hybridization (aCGH). CTCs from nine (9) patients successfully profiled were observed to have multiple copy number aberrations including those previously reported in primary prostate tumors such as gains in 8q and losses in 8p. High-level copy number gains at the androgen receptor (AR) locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs and archival primary tumors from the same patients revealed common lineage. However, high-level copy number gains in the AR locus were observed in CTCs, but not in the matched archival primary tumors. We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in

  17. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Liang Y

    2016-05-01

    Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Johannes D Aebi,2 Salman M Hyder1 1Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA; 2Medicinal Chemistry, Roche Pharma Research and Early Development (pRED, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland Abstract: Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration; however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylaminohexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071 (RO, which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway, on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the

  18. 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 ...

  19. 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 with...

  20. Cabazitaxel: A novel taxane for metastatic castration-resistant prostate cancer-current implications and future prospects

    Directory of Open Access Journals (Sweden)

    Afroz Abidi

    2013-01-01

    Full Text Available Recent advances in the management of prostate cancer have shown considerable development with time and many novel therapeutic agents have been approved over the past years. For patients with metastatic castration-resistant prostate cancer (mCRPC, initially docetaxel was the standard chemotherapy but once they became refractory to docetaxel, no treatment improved survival. This scenario changed in June 2010 when the US Food and Drug Administration (FDA approved Cabazitaxel as a new therapeutic option for patients with mCRPC resistant to docetaxel. Cabazitaxel, being a novel tubulin-binding taxane with poor affinity for P-glycoprotein, decreases the chances of resistance. It has shown antitumor activity in preclinical, phase I, II and III clinical studies in docetaxel-resistant tumors. This article summarises the background, pharmacodynamic, kinetics and clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer. Future development and rational use of this drug in other tumors is under therapeutic investigation.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...... 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....

  6. 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...

  7. 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

  8. 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.

  9. Toward a Common Therapeutic Framework in Castration Resistant Prostate Cancer: A Model for Urologic Oncology and Medical Oncology Interaction

    OpenAIRE

    de Vere White, Ralph; Lara, Primo N.

    2014-01-01

    The rapid evolution of palliative therapeutic choices in the last few years for patients with advanced castration resistant prostate cancer (CRPC) has resulted in a dilemma currently troubling a few other epithelial malignancies: which systemic agent to choose and at what time? In addition, which specialty specifically directs the delivery of such care – Urology or Medical Oncology – has not been clearly established. Recognizing the lack of consensus, we propose a framework for Urology and Me...

  10. 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.

  11. 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

  12. 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.

  13. Downregulation of c-SRC kinase CSK promotes castration resistant prostate cancer and pinpoints a novel disease subclass.

    Science.gov (United States)

    Yang, Chih-Cheng; Fazli, Ladan; Loguercio, Salvatore; Zharkikh, Irina; Aza-Blanc, Pedro; Gleave, Martin E; Wolf, Dieter A

    2015-09-01

    SRC kinase is activated in castration resistant prostate cancer (CRPC), phosphorylates the androgen receptor (AR), and causes its ligand-independent activation as a transcription factor. However, activating SRC mutations are exceedingly rare in human tumors, and mechanisms of ectopic SRC activation therefore remain largely unknown. Performing a functional genomics screen, we found that downregulation of SRC inhibitory kinase CSK is sufficient to overcome growth arrest induced by depriving human prostate cancer cells of androgen. CSK knockdown led to ectopic SRC activation, increased AR signaling, and resistance to anti-androgens. Consistent with the in vitro observations, stable knockdown of CSK conferred castration resistance in mouse xenograft models, while sensitivity to the tyrosine kinase inhibitor dasatinib was retained. Finally, CSK was found downregulated in a distinct subset of CRPCs marked by AR amplification and ETS2 deletion but lacking PTEN and RB1 mutations. These results identify CSK downregulation as a principal driver of SRC activation and castration resistance and validate SRC as a drug target in a molecularly defined subclass of CRPCs. PMID:26091350

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

    International Nuclear Information System (INIS)

    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. 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. 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

  15. Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats

    International Nuclear Information System (INIS)

    Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further tested with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues

  16. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm3 vs. 1195 ± 84 mm3, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

  17. 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

  18. 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

  19. 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

  20. [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

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Mehta, Amit R; Armstrong, Andrew J

    2016-02-01

    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

  4. 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.

  5. 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

  6. Impact of castration with or without alpha-tocopherol supplementation on the urethral sphincter of rats

    Directory of Open Access Journals (Sweden)

    Mirian Kracochansky

    2012-04-01

    Full Text Available OBJECTIVE: To analyze the impact of low levels of testosterone induced by orchiectomy and the effect of alpha-tocopherol supplementation on oxidative stress in the urethral sphincter. MATERIALS AND METHODS: Forty male Wistar rats weighing 250-300g were divided into four groups with 10 each: Sham group; Orchiectomy group: bilateral orchiectomy; Orchiectomy-pre-Tocopherol group: bilateral orchiectomy preceded by alpha-tocopherol supplementation for four weeks; Orchiectomy-full-Tocopherol group: bilateral orchiectomy with alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the protocol end, animals were euthanized and had the sphincter analyzed stereologically focusing on collagen and muscle fibers percentage. Oxidative stress levels were determined using 8-epi-PGF2. RESULTS: The 8-epi-PGF2 levels were statistically higher (p < 0.0003 in the Orchiectomy group compared to others groups while Sham and Orchiectomy-full-Tocopherol groups presented statistically similar values (p = 0.52. Collagen volumetric densities were significantly lower in Sham and Orchiectomy-full-Tocopherol groups (p < 0.022. Sham group presented statistically greater muscle fiber percent. CONCLUSION: Castration caused oxidative stress in the urethral sphincter complex, with increased collagen deposition. Alpha-tocopherol had a protective effect and its supplementation for twelve weeks provided the greatest protection.

  7. 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

  8. The Role of Palliative Surgery in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Heidenreich, Axel; Porres, Daniel; Pfister, David

    2015-01-01

    Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) analogues or antagonists represents the treatment of choice in men with metastatic prostate cancer (PCA). Depending on the serum concentration of the prostate-specific antigen (PSA) nadir, the survival might vary between 11 and 78 months. In castration-resistant PCA (CRPC), all new medical treatment options can induce complete and partial remissions in metastatic foci, but they have no profound effect on the prostate itself, as has been shown recently. About one-third of all patients without local treatment of the primary will develop significant complications of the lower and upper urinary tract due to local progression of the PCA. In men with CRPC and lower urinary tract symptoms, palliative transurethral resection of the prostate (TURP) can be performed with a 60-70% success rate. Infiltration of the pelvic floor, the bladder neck and trigone, and the external urethral sphincter can make palliative radical surgery necessary. Bladder neck closure with continent vesicostomy, radical cystoprostatectomy with an incontinent urinary diversion, and anterior and posterior exenteration are individual therapeutic options in men with a good performance status and a considerable life expectancy. Symptomatic involvement of the upper urinary tract can be managed by the placement of endoluminal stents or a percutaneous nephrostomy in men with poor performance. In men with a good response to ADT and a good performance status, reconstructive ureteral surgery might be considered and the options of ureteral reimplantation, ureter ileal replacement, and a subcutaneous pyelovesical bypass have to be discussed. The indication to perform one of the above-mentioned surgical approaches needs to be discussed in a multidisciplinary tumor board. PMID:26632812

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Aucoin, Michael William; Wassersug, Richard Joel

    2006-12-01

    Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste. PMID:16989928

  12. Proteins of the rat prostate. II. Synthesis of new proteins in the ventral lobe during castration-induced regression

    International Nuclear Information System (INIS)

    Ventral prostates from adult Sprague-Dawley rats at different days postcastration were cut into one to two mm.3 pieces and incubated in medium containing S-35-methionine (100 uCi/ml.) at 37 C under 95% oxygen and 5% carbon dioxide for four hours. The incubated tissues were subjected to two-dimensional electrophoresis and radiofluorography. Over 100 spots were developed in the fluorograms. Three groups of spots, representing cytoskeletal proteins, androgen-dependent proteins and castration-induced proteins, were further evaluated by a computer-based densitometer. The level of densitometry absorption is proportional to the amount of radioactivity in each spot. The synthesis of cytoskeletal proteins, such as actin and tropomyosin, were relatively constant throughout the course of prostatic regression. The rate of synthesis of androgen-dependent proteins declined rapidly from a high level of synthesis before castration to a non-detectable level by Day 3 postcastration. However, three proteins, which were either not synthesized (spot G and spot H) or synthesized at a very low level (spot I) before castration, were the major proteins synthesized by the prostate during early stages of its regression. The rate of synthesis of these proteins reached a peak by Day 4 postcastration, declined rapidly and remained at a low level thereafter. The respective molecular weights and isoelectric points for these three proteins were 33 Kd and 7.2 for spot G, 38 Kd and 5.3 for spot H and 64 Kd and 6.0 for spot I. Previous findings showed that prostatic regression in rats was associated with a surge of activities in proteolytic enzymes which peaked five to six days postcastration

  13. 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

  14. 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

  15. 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) ...

  16. 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?

  17. 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...

  18. 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...

  19. 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.

  20. 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

  1. 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...

  2. 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

  3. 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

  4. An update on TroVax® for the treatment of progressive castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Abern M

    2011-05-01

    Full Text Available Michael Abern1, Howard L Kaufman2, Kalyan Latchamsetty11Department of Urology, Rush University Medical Center, Chicago, IL, USA; 2Department of General Surgery and Immunology and Microbiology, Rush University Medical Center, Chicago, IL, USAAbstract: Prostate cancer is a common human malignancy with few effective therapeutic options for treating advanced castration-resistant disease. The potential therapeutic effectiveness of immunotherapy and vaccines, in particular, has gained popularity based on the identification of prostate-associated antigens, potent expression vectors for vaccination, and data from recent clinical trials. A modified vaccinia Ankara (MVA virus expressing 5T4, a tumor-associated glycoprotein, has shown promise in preclinical studies and clinical trials in patients with colorectal and renal cell carcinoma. This review will discuss the rationale for immunotherapy in prostate cancer and describe preclinical and limited clinical data in prostate cancer for the MVA-5T4 (TroVax® vaccine.Keywords: castration resistance, prostate cancer, TroVax, vaccine

  5. 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.

  6. 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

  7. Effects of a7nAChR agonist on the tissue estrogen receptor expression of castrated rats

    Science.gov (United States)

    Ma, Feng; Gong, Fan; Lv, Jinhan; Gao, Jun; Ma, Jingzu

    2015-01-01

    Osteoporosis is one common disease in postmenopausal women due to depressed estrogen level. It has been known that inflammatory factors are involved in osteoporosis pathogenesis. One regulator of inflammatory cascade reaction, a7-nicotinic acetylcholine receptor (a7nAChR), therefore, may exert certain role in osteoporosis. This study thus investigated this question on an osteoporosis rat model after castration. Rats were firstly castrated to induce osteoporosis, and then received a7nAChR agonist (PNU-282987), diethylstilbestrol or saline via intraperitoneal injection. After 6 or 12 weeks, bone samples were collected for counting osteoblast number, bone density and estrogen receptor (ERα and ERβ) expression, in addition to the serum laboratory of inflammatory factors. Bone density, osteoclast number, ERα and ERβ expression level were significantly depressed in model group, and were remarkable potentiated in the drug treatment group (P<0.05). The levels of BGP and PTH in drug treatment group were decreased compared to diethylstilbestrol group, while E2 and IGF-1 showed up-regulation. Agonist of a7nAChR can up-regulate estrogen receptor expression and may prevent the occurrence and development of osteoporosis. PMID:26722551

  8. Circulating endothelial progenitor cells in castration resistant prostate cancer: a randomized, controlled, biomarker study.

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    Thorsten Fuereder

    Full Text Available BACKGROUND: Endothelial progenitor cells (CEPs and circulating endothelial cells (CECs are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC patients. PATIENTS AND METHODS: Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d, in combination with docetaxel (75 mg/m2 or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy. RESULTS: A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001. However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30% patients responded to therapy with a 50% PSA decline, while 9 (64% patients showed a PSA decline in the combination group (n.s.. The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062 in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable. CONCLUSION: In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However

  9. 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

  10. 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…

  11. 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

  12. Effects of ractopamine administration and castration method on muscle fiber characteristics and sensory quality of the longissimus muscle in two Piétrain pig genotypes.

    Science.gov (United States)

    Li, Hui; Gariépy, Claude; Jin, Ye; Font I Furnols, Maria; Fortin, Jacinthe; Rocha, Luiene M; Faucitano, Luigi

    2015-04-01

    Single and combined effects of ractopamine supplementation (RAC, 7.5 vs. 0 ppm), castration method (surgical castration: SC vs. immuno-castration: IM) and genotype (genotype A: GA vs. GB containing 25% or 50% Piétrain) were determined on longissimus muscle (LM) fiber traits and quality of pork (n=512). RAC increased fiber IIX cross-sectional area (P=0.009) and decreased glycolytic potential (P=0.02) and pork tenderness (P<0.001). Fiber traits indicated that LM of IM pigs was more oxidative (P<0.05) and meat had slightly higher (P=0.04) off-flavor score and WBSF than SC. LM from GB pigs was paler (P<0.05) and had greater (P<0.05) glycolytic potential, IIX fiber cross sectional area and pork off-flavor than GA. RAC supplementation, castration method and genotype or their combination affected some fiber traits and some quality parameters but differences reported were small indicating these treatments or their combination could be used without major prejudice to meat quality. PMID:25529286

  13. 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...

  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

    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

  15. 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

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

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    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

  17. 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...

  18. Effect of feed restriction on the performance and behaviour of pigs immunologically castrated with Improvac®.

    Science.gov (United States)

    Quiniou, N; Monziols, M; Colin, F; Goues, T; Courboulay, V

    2012-09-01

    For centuries, entire male pigs have been castrated to reduce the risk of boar taint. However, physical castration of pig is increasingly being questioned with regard to animal welfare considerations. Immunization against gonadotrophin releasing hormone (GnRH) provides an alternative to physical castration. Using the currently available commercial product (Improvac®; Pfizer Animal Health), a two-dose regimen of a GnRH vaccine is administered. After the second vaccination, a substantial increase in feed consumption has been reported, which may be associated with increased body fatness and decreased feed efficiency when compared with unvaccinated entire male pigs. The aim of the present study was to investigate the effect of a feed restriction on these traits and on the behaviour of 120 group-housed entire males (five pigs/pen) vaccinated against GnRH. The first vaccination was performed at 62 days of age and the second (V2) at 130 days of age. Pigs were slaughtered in two batches 4 to 5 weeks after V2. They were either offered feed ad libitum over the 22 to 114 kg BW range (AL treatment) or ad libitum up to a maximum of 2.50 (R2.50 treatment) or 2.75 kg/day per pig (R2.75 treatment). Behavioural observations and skin lesion scoring were conducted 1 week before V2, and 1 and 3 weeks after V2. At slaughter, the volumetric lean meat content was measured using an X-ray computed tomography scanner. Between V2 and slaughter, the average feed intakes for the R2.75 and R2.50 treatments were 15% and 22% lower than the average AL feed intake (3.20 kg/day), respectively. Feed restriction was associated with a reduced average daily gain after V2 (846, 932 and 1061 g/day in the R2.50, R2.75 and AL groups, P meat content (71.8%, 70.7% and 70.4% in the R2.50, R2.75 and AL groups, P = 0.14), despite a reduced backfat thickness measured in restrictively fed pigs (12.0, 13.0 and 13.6 mm in the R2.50, R2.75 and AL groups, P < 0.01). Higher skin lesion scores were observed 3 weeks

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

    Science.gov (United States)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette; Bisbjerg, Rasmus; Daugaard, Gedske; Sengeløv, Lisa

    2016-08-01

    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 with second-line and third-line CA (P=0.483). Events with grade 3-4 nonhematological toxicity were equally distributed in the two groups (32 vs. 35%, P=0.80). PSA responses were observed in 46 and 17% of patients treated with second-line and third-line CA (P=0.002). PFS (5.5 vs. 3.3 months, P=0.087, log rank) and OS (18.3 vs. 11.4 months, P=0.003, log rank) was longer in patients treated with second-line CA. OS measured from second-line abiraterone acetate/enzalutamide was similar (18.0 months) to second-line CA (P=0.883, log rank). Treatment-related toxicity was independent of CA being administered as second-line or third-line therapy. Although PFS and the frequency of PSA responders favored patients treated with second-line CA, one treatment sequence could not be considered superior to the other in this study. PMID:27148775

  20. Desempenho produtivo, características de carcaça e avaliação econômica de bovinos cruzados, castrados e não-castrados, terminados em pastagens de Brachiaria decumbens Productive performance, carcass characteristics and economic evaluation of castrated and non-castrated crossbred bovines finished in Brachiaria decumbens pastures

    Directory of Open Access Journals (Sweden)

    L.C.V. Ítavo

    2008-10-01

    Full Text Available Avaliou-se o efeito da castração sobre o desempenho produtivo e sobre as características de carcaça e realizou-se a avaliação econômica de bovinos terminados em pastagens de Brachiaria decumbens. Foram utilizados oito novilhos Canchim-Nelore com 14 meses de idade, sendo quatro animais castrados e quatro não-castrados, com média de peso corporal de 273,2kg. O delineamento foi inteiramente ao acaso com quatro repetições por tratamento. Os animais receberam, diariamente, 0,7% do PC de suplemento proteíco-energético e foram abatidos aos 26 meses de idade. O peso de abate e o ganho médio diário (GMD diferiram entre castrados e não-castrados, com médias de 441,0 e 482,2kg e 0,6 e 0,7kg/dia, respectivamente. Não houve efeito da castração sobre as características avaliadas, com exceção do peso de abate, do peso da carcaça quente, 252,3 versus 229,9kg, da cor da carne, 3,25 versus 4,50 pontos e da espessura da gordura subcutânea, 0,6 versus 1,4mm, respectivamente, para não-castrados e castrados. A lucratividade por animal e por hectare foi de 14,5 e 15,8% para não-castrados e 4,5 e 5,8% para castrados, respectivamente. Sugere-se a utilização de bovinos não-castrados suplementados em pastagens de Brachiaria decumbens.The effect of the castration on the productive performance and carcass characteristics was studied, as well as, the economic evaluation of finished bovines raised on Brachiaria decumbens pastures. Eight Canchim-Nellore steers aging 14-months-old were used, being four castrated and four non-castrated, averaging 273.2kg body weight. It was used a completely randomized design with four repetitions per treatment. The animals received 0.7% of their body weight of proteic-energetic supplement and were slaughtered at 26 months of age. The weight at slaughtering and the average daily weight gain differed between castrated and non-castrated, averaging 441.0 and 482.2kg, and 0.6 and 0.7kg/day, respectively. No effects of

  1. 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.

  2. CHARACTERISTICS OF CARCASS AND MEAT IN CASTRATED OR NON CASTRATED NELORE BREED HEIFERS CARACTERÍSTICAS DE CARCAÇA E CARNE EM NOVILHAS CASTRADAS OU NÃO-CASTRADAS DA RAÇA NELORE

    Directory of Open Access Journals (Sweden)

    Klaito José Gonçalves dos Santos

    2007-12-01

    Full Text Available

    This study aimed to evaluate the effect of the la-tex ring applied on the ovarian pedicle, in Nelore breed heifers destined to slaughter, on the carcass and meat cha-racteristics. 23 Nelore female bovines were used in this study, eight months old (±2 and medium weight of 130 kg (±10 kept in Brachiaria            brizantha pasture and energetic mineralized salt supplementation, randomly distributed in two groups. The group I (GI was constituted by 11 heifers castrated with by the application of the latex ring on the ovarian pedicle and the group II (GII was composed by 12 non castrated heifers. The slaughter occurred when the animals reached the medium weight of 325 kg (±20, between 28 and 30 months old and the parameters cold carcass height, weight of the thoracic and pelvic quarters, side cut, loin eye area, thickness of fat tissue and sleek-ness of the meat. The latex ring applied on the ovarian pedicle in Nelore breed heifers did not influence positively the carcass and meat characteristics but the loin eye area, which was favorable to the non castrated ones.

    Key-words: Bovines, carcass, meat, latex ring, ovary.

    Neste trabalho avaliou-se o efeito do anel de látex aplicado no pedículo ovariano, em bezerras da raça Nelore destinadas ao abate, sobre as características de carcaça e carne. Para tanto, utilizaram-se 23 fêmeas da raça Nelore, na faixa etária de oito meses (±2 e peso médio de 130 kg (± 10, mantidas à pastagem de Brachiaria   brizantha e suplementada com sal mineralizado energético e protéi-co. Distribuíram-se esses animais aleatoriamente em dois grupos, sendo o grupo I (GI constituído por onze bezerras castradas com anel de látex aplicado no pedículo ovariano e o grupo II (GII formado por doze bezerras não submetidas a nenhum método de esterilização. O abate ocorreu quando os animais atingiram peso médio de 325 kg

  3. 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

  4. Effects of feeding ractopamine hydrochloride (Paylean) to physical and immunological castrates (Improvest) in a commercial setting on growth performance and carcass characteristics.

    Science.gov (United States)

    Lowe, B K; Gerlemann, G D; Carr, S N; Rincker, P J; Schroeder, A L; Petry, D B; McKeith, F K; Allee, G L; Dilger, A C

    2014-08-01

    Growth performance and carcass characteristics of physically castrated (PC) and immunologically castrated (IC) pigs fed ractopamine hydrochloride (RAC; 5 mg/kg) were evaluated in 64 pens of 22 pigs each. Male pigs were randomly assigned to castration method at birth. Pigs in the PC group were physically castrated at 5 d of age while IC pigs were administered Improvest at 11 and 18 wk of age. Pigs entered the grow-finish barn at approximately 9 wk of age (d 0). Dietary treatments (control or RAC) were initiated on d 87. Final treatment arrangement was a 2 × 2 factorial of castration method and diet. Data were analyzed using a mixed model with fixed effects of castration method, diet, market group, and all 2- and 3-way interactions. Pen was the experimental unit. From d 0 to 65, IC pigs had 11.2% greater (P < 0.01) G:F and 11.6% less (P < 0.01) ADFI than PC pigs, but ADG was increased 1.0% in PC pigs compared with IC pigs (P < 0.01). From d 65 to 87, IC pigs had 7.9% greater (P < 0.01) ADG and 12.1% greater (P < 0.01) G:F than PC pigs while having similar (P = 0.16) ADFI. At the initiation of diet (RAC) treatments, BW of all treatments were similar (P ≥ 0.32). From d 87 to 120 (RAC feeding period), IC pigs had 10.0% greater (P < 0.01) ADG and 10.5% greater (P < 0.01) ADFI than PC pigs while having similar (P = 0.64) G:F. Feeding RAC increased (P < 0.01) ADG by 16.9% and G:F by 17.9% while having no effect (P = 0.42) on ADFI from d 87 to 120. There were no significant interactions between castration method and diet on growth performance from d 87 to 120. For the entire study (d 0-120), IC pigs had 2.6% greater (P < 0.01) ADG, 4.6% less (P < 0.01) ADFI, and 7.3% greater (P < 0.01) G:F than PC pigs. Averaged over market groups, IC pigs were 2.5 kg heavier (P < 0.01) and had similar (P = 0.10) carcass weights and 1.8 percentage units less (P < 0.01) dressing yields than PC pigs. Additionally, IC pigs had 1.3 mm less (P < 0.01) fat and 1.7 mm less (P < 0.01) loin depth

  5. 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

  6. 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

  7. 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

  8. 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-...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes

    OpenAIRE

    Fredericks, William J.; Sepulveda, Jorge; Lal, Priti; Tomaszewski, John E.; Lin, Ming-Fong; McGarvey, Terry; Rauscher, Frank J.; Malkowicz, S. Bruce

    2013-01-01

    Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phe...

  15. CONTROLLING ANTLER GROWTH IN A CASTRATED INDOCHINESE SIKA DEER CERVUS NIPPON PSEUDAXIS USING A COMMERCIALLY AVAILABLE TRENBOLONE ACETATE AND ESTRADIOL IMPLANT.

    Science.gov (United States)

    Raines, Janis A; Storms, Timothy

    2015-12-01

    A captive Indochinese sika deer (Cervus nippon pseudaxis) was castrated at the age of 5 yr. The resultant abnormal antler growth over the next few years became difficult to manage from both the veterinary and husbandry standpoints. Using a commercially available trenbolone acetate and estradiol implant marketed for domestic cattle heifers, normal mineralization of the abnormal antlers was achieved along with the expected normal casting. The deer was then maintained for 6 yr using an annual implant regimen. PMID:26667563

  16. Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial

    OpenAIRE

    Cella, D; Ivanescu, C; Holmstrom, S.; Bui, C. N.; Spalding, J.; Fizazi, K.

    2014-01-01

    Background To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial. Patients and methods Patients were randomly assigned to enzalutamide 160 mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study tre...

  17. 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 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

  18. Effects of immunological castration (Improvest) on further processed belly characteristics and commercial bacon slicing yields of finishing pigs.

    Science.gov (United States)

    Kyle, J M; Bohrer, B M; Schroeder, A L; Matulis, R J; Boler, D D

    2014-09-01

    Objectives were to compare fresh belly characteristics, further processed belly characteristics, and commercial bacon slicing yields of immunologically castrated (IC) barrows, IC barrows fed ractopamine hydrochloride (IC+RAC), physically castrated (PC) barrows, intact males, and gilts. One hundred eighty-eight bellies from pigs housed in single sex pens (n = 48) slaughtered at 130 kg ending live weight were evaluated for flop distance, length, width, thickness, and fatty acid composition. Bellies were injected, thermally processed, and sliced according to standard protocols at a USDA federally inspected facility. Complete slices were sorted by trained plant personnel. Then, sliced bellies were individually packaged to maintain anatomical orientation. The effects of treatments were analyzed as a generalized linear mixed model with pen of pigs serving as the experimental unit for all comparisons. Belly thickness was not different (P ≥ 0.11) in bellies from IC barrows (3.74 cm) compared with bellies from IC+RAC (3.60 cm), PC barrows (3.94 cm), or gilts (3.64 cm); however, bellies were 0.42 cm thicker (P < 0.01) in IC barrows compared with intact males. Iodine value was not different (P ≥ 0.06) in bellies from IC barrows (68.26) compared with bellies from IC+RAC (69.78), PC barrows (67.55), or gilts (69.45); however, iodine value was 2.32 units less (P < 0.01) in IC barrows compared with intact males. Green weight was not different (P ≥ 0.09) in bellies from IC barrows (4.88 kg) compared with bellies from IC+RAC (5.11 kg), PC barrows (5.10 kg), or gilts (4.79 kg); however, green weight was 0.56 kg greater (P < 0.0001) in IC barrows compared with intact males. Pump uptake and cooked yield was not different (P ≥ 0.15) among treatment groups. Slicing yield (as a percentage of green weight) was decreased (P ≤ 0.01) in bellies from IC barrows (93.61%) compared with bellies from PC barrows (98.42%) or gilts (98.19%); however, slicing yield was not different (P

  19. Phase I Study of the Prolactin Receptor Antagonist LFA102 in Metastatic Breast and Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Machiels, Jean-Pascal; Suárez, Cristina; Lewis, Nancy; Higgins, Michaela; Wisinski, Kari; Awada, Ahmad; Maur, Michela; Stein, Mark; Hwang, Andy; Mosher, Rebecca; Wasserman, Ernesto; Wu, Gang; Zhang, Hefei; Zieba, Renata; Elmeliegy, Mohamed

    2016-01-01

    Lessons Learned Despite evidence for a role for prolactin signaling in breast and prostate tumorigenesis, a prolactin receptor-binding monoclonal antibody has not produced clinical efficacy. Increased serum prolactin levels may be a biomarker for prolactin receptor inhibition. Results from the pharmacokinetic and pharmacodynamics (PD) studies suggest that inappropriately long dosing intervals and insufficient exposure to LFA102 may have resulted in lack of antitumor efficacy. Based on preclinical data, combination therapy of LFA102 with those novel agents targeting hormonal pathways in metastatic castration-resistant prostate cancer and metastatic breast cancer is promising. Given the PD evidence of prolactin receptor blockade by LFA102, this drug has the potential to be used in conditions such as hyperprolactinemia that are associated with high prolactin levels. Background. Prolactin receptor (PRLR) signaling is implicated in breast and prostate cancer. LFA102, a humanized monoclonal antibody (mAb) that binds to and inhibits the PRLR, has exhibited promising preclinical antitumor activity. Methods. Patients with PRLR-positive metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) received doses of LFA102 at 3–60 mg/kg intravenously once every 4 weeks. Objectives were to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) to investigate the safety/tolerability of LFA102 and to assess pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity. Results. A total of 73 patients were enrolled at 5 dose levels. The MTD was not reached because of lack of dose-limiting toxicities. The RDE was established at 60 mg/kg based on PK and PD analysis and safety data. The most common all-cause adverse events (AEs) were fatigue (44%) and nausea (33%) regardless of relationship. Grade 3/4 AEs reported to be related to LFA102 occurred in 4% of patients. LFA102 exposure increased approximately dose

  20. Effects of estrogens, clomiphene and castration in a male transsexual with as compared to those without hypersecretion of gonadotropins.

    Science.gov (United States)

    Goh, H H; Ratnam, S S

    1990-06-01

    A 24-year-old male-to-female transsexual with hypersecretion of gonadotropins was studied with regard to his recovery from sex steroid hormone treatment before his sex change operation and the effects of castration, clomiphene tests and estrogens on the hypersecretion of gonadotropins. Computer-assisted tomography and X-ray results indicated that the possibility that the hypersecretion of gonadotropins was not associated with a pituitary adenoma could not be ruled out. After a period of recovery from previous sex steroid hormone therapy, inappropriately high FSH and LH levels in the presence of normal male levels of testosterone and estradiol were found. The latter normal levels failed to suppress both the FSH and LH levels. From the clomiphene challenge tests carried out before and after the sex reassignment operation, the estradiol infusion studies and treatment with ethinyl estradiol after the sex reassignment operation, it appears that the hypersecretion of gonadotropins was responsive to the negative feedback effect of estrogens. However, the sensitivity, especially that of FSH, was very attenuated. Even after 23 weeks of ethinyl estradiol treatment FSH remained well above the upper limit for normal men. The results showed that before his sex change operation the hypersecretion of gonadotropins in the patient was probably under autonomous control. Testicular factors at normal male concentrations appear to have a minimal negative feedback effect on the hypersecretion of gonadotropins. However, hypersecretion of gonadotropins can be suppressed by prolonged exposure to estrogens. PMID:2118708

  1. 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

  2. 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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes.

    Science.gov (United States)

    Zhong, Di; Zhang, Hui-Jian; Jiang, Yao-Dong; Wu, Peng; Qi, Huan; Cai, Chao; Zheng, Shao-Bin; Dang, Qiang

    2016-06-10

    Androgen deprivation therapy is the gold standard regimen for advanced Prostate cancer (PCa) patients, nevertheless, patients eventually develop into castration-resistant prostate cancer (CRPC). Currently only a few chemotherapeutics are available for CRPC. Therefore, it is critical for identifying a new drug. In this study, we will explore a new agent, Saikosaponin-d (SSd), for CRPC therapy based on its mechanism of action. DU145 and CWR22Rv1 cells representing CRPC were employed in this study. A series of cell, biochemical, and molecular biologic assays such as Immunofluorescence, Zymography, Sphere formation, Colony formation, and MTT were used. Finally, we find SSd can significantly inhibit the growth of PCa cells in both dose- and time-dependent and suppress the colony formation during a long-term drug administration, it also can inhibit their migration and invasion abilities, which was accompanied by reverse the epithelial-mesenchymal transition (EMT) and suppress MMP2/9 expression as well as activities. Furthermore, SSd can suppress cancer stem cell (CSC) phenotypes such as self-renewal ability. Mechanistically, SSd blocks Wnt/β-catenin signaling pathway by decreasing GSK3β phosphorylation to affect EMT and CSC. These findings demonstrate the mechanism of anti-cancer activity of SSd in targeting EMT and CSC, suggesting SSd can be a potent agent for CRPC therapy. PMID:27155154

  6. Effects of ractopamine on growth performance and carcass characteristics of immunologically and physically castrated barrows and gilts.

    Science.gov (United States)

    Puls, C L; Ellis, M; McKeith, F K; Gaines, A M; Schroeder, A L

    2014-10-01

    The study was performed to evaluate the effect of feeding ractopamine (RAC) to physically castrated barrows (PC), immunologically castrated barrows (IC), and gilts (gilts) using a randomized complete block design with a 3 × 3 factorial arrangement of treatments: 1) sex (PC, IC, and gilts) and 2) RAC inclusion level (0, 5, and 7.5 mg/kg). The IC received 2 doses of gonadotropin releasing factor analog-diphtheria toxoid conjugate (Improvest; Zoetis, Kalamazoo, MI) at the start of the study (wk 16 of age; 69.6 ± 2.96 kg BW) and 4 wk later. The study used 180 pigs housed in groups of 4 (5 groups/sex × RAC subclass) and was performed over a fixed time of 61 d with RAC being fed for the final 26 d of study. Diets were formulated to meet requirements of intact males for the first 35 d and of intact males fed 7.5 mg/kg RAC for the remainder of the study. Pigs had ad libitum access to feed and water throughout the study period. At the end of the study, pigs were harvested at a commercial facility and HCW and last rib backfat thickness were measured. There were no treatment interactions (P > 0.05) for any variables. For the overall study period, IC had greater (P ≤ 0.05) overall ADG compared to PC, which grew faster (P ≤ 0.05) than gilts (1,246, 1,083, and 1,025 g/d for IC, PC, and gilts, respectively; SEM = 20.3); ADFI was lower (P ≤ 0.05) for gilts than IC and PC, which had similar ADFI (3.36, 3.37, and 2.87 kg/d, respectively; SEM = 0.051); and G:F was greater (P ≤ 0.05) for IC than gilts and greater for gilts than PC (0.371, 0.322, and 0.358 kg/kg, respectively; SEM = 0.0039). For the period from the second dose to the end of study, IC had greater (P ≤ 0.05) ADG (28.6%), ADFI (12.3%), and G:F (14.3%) than PC. Carcass yield was lower (P ≤ 0.05) for IC compared to PC and gilts (72.8, 75.0, and 74.6%, respectively; SEM = 0.25). Feeding RAC increased (P ≤ 0.05) ADG (15.7 and 14.5% for 5 and 7.5 mg/kg, respectively), G:F (17.1 and 16.4%, respectively

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

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

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    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.

  13. LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer

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    Marra Marco A

    2010-09-01

    Full Text Available Abstract Background There is no cure for castration-recurrent prostate cancer (CRPC and the mechanisms underlying this stage of the disease are unknown. Methods We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC in vivo using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC. Results Three million tags were sequenced using in vivo samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (CCNH, CUEDC2, FLNA, PSMA7, steroid synthesis and metabolism (DHCR24, DHRS7, ELOVL5, HSD17B4, OPRK1, neuroendocrine (ENO2, MAOA, OPRK1, S100A10, TRPM8, and proliferation (GAS5, GNB2L1, MT-ND3, NKX3-1, PCGEM1, PTGFR, STEAP1, TMEM30A, but neither supported nor discounted a role for cell survival genes. Conclusions The in vivo gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.

  14. 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

  15. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Chi, Kim N; Spratlin, Jennifer; Kollmannsberger, Christian; North, Scott; Pankras, Catherine; Gonzalez, Martha; Bernard, Apexa; Stieltjes, Hans; Peng, Lixian; Jiao, James; Acharya, Milin; Kheoh, Thian; Griffin, Thomas W; Yu, Margaret K; Chien, Caly; Tran, Nam Phuong

    2015-12-01

    Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients. Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0.5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety. PMID:26096139

  16. 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

  17. 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...

  18. 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...

  19. 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...

  20. Effects of ractopamine administration and castration method on the response to preslaughter stress and carcass and meat quality in pigs of two Piétrain genotypes

    OpenAIRE

    Rocha, L. M.; Bridi, A.M.; Foury, Aline; Mormède, Pierre; Weschenfelder, A. V.; Devillers, N.; Bertoloni, W.; Faucitano, Luigi

    2013-01-01

    The objective of this study was to evaluate the effects of ractopamine supplementation, castration method, and their interaction on the behavioral and physiological response to preslaughter stress and carcass and meat quality of 2 Piétrain genotypes. A total of 1,488 male pigs (115 ± 5 kg BW) were distributed according to a 2 × 2 × 2 factorial arrangement of treatments. The first factor was ractopamine supplementation with 2 groups of pigs (376 and 380 pigs each) receiving 7.5 mg/kg of ractop...

  1. Effects of feeding ractopamine hydrochloride (Paylean) to physical and immunological castrates (Improvest) in a commercial setting on carcass cutting yields and loin quality.

    Science.gov (United States)

    Lowe, B K; Gerlemann, G D; Carr, S N; Rincker, P J; Schroeder, A L; Petry, D B; McKeith, F K; Allee, G L; Dilger, A C

    2014-08-01

    Effects of feeding ractopamine (RAC; 5 mg/kg) to physically castrated (PC) and immunologically castrated (IC) pigs on carcass characteristics, cutting yields, and loin quality were evaluated using 285 carcasses. Male pigs were randomly assigned to sex treatments (PC and IC) at birth and fed the same nursery diets before allotment into 32 pens with 22 pigs per pen in a grow-finish barn. Pigs in the PC group were physically castrated at approximately 5 d of age, and pigs in the IC group were administered Improvest at 11 and 18 wk of age. Diet treatments (control or RAC) were initiated on study d 87. Pigs were marketed at 12 d (4.5 wk post-second Improvest dose), 19 d (5.5 wk post-second Improvest dose), and 33 d (7.5 wk post-second Improvest dose) following the start of final diet treatments. Three carcasses per pen were selected for evaluation of cutting yields and loin quality. Data were analyzed using PROC MIXED in SAS with fixed effects of sex, diet, market group, and their interaction; carcass (N = 285) was the experimental unit. Carcasses from RAC-fed pigs were heavier (P 0.05) between RAC-fed and control-fed carcasses when evaluating LM color, marbling, firmness, pH, drip loss, and tenderness. Carcasses from IC pigs had greater (P < 0.05) boneless lean yields, bone-in lean yields, and total carcass cutting yields than PC carcasses. There were minimal differences (P < 0.05) in LM marbling, firmness, composition, and tenderness between PC and IC pigs. There was an interaction (P = 0.03) between sex and diet for LM composition. Control-fed PC loins had more (P < 0.01) lipid than all other treatment combinations. Market group had effects (P < 0.05) on carcass cutting yields, LM color, marbling and firmness scores, pH, purge loss, composition, and tenderness. The results from this study indicated RAC and immunological castration were additive in terms of improving carcass cutting yields while having minimal effects on pork quality. PMID:25006065

  2. [Effect of amino acid supplements to barley meal on the nitrogen metabolism of growing castrated male swine (20-65 kg live weight)].

    Science.gov (United States)

    Wecke, C; Gebhardt, G

    1981-03-01

    In 56 N-balance experiments of the influence of differentiated amino acid supplements to coarse barley meal enriched with energy, minerals and additives on the nitrogen metabolism of castrated male pigs, was investigated. The joint supplement of lysine and methionine remained without result in comparison with the sole supplementation of lysine. Only the additional supplementation of threonine resulted in the further improvement of protein utilisation. The results corroborate the effect of the amino acid lysine limiting the performance in barley protein and prove that threonine takes the second place in the sequence of limitation. PMID:6791610

  3. Prostate cancer with lytic bone metastases: 18F-fluorodeoxyglucose positron emission tomography-computed tomography for diagnosis and monitoring response to medical castration therapy

    International Nuclear Information System (INIS)

    Lytic bone metastases are rare in prostate cancer. We here present 18 fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) images of a 67-year-old male patient with lytic metastases from prostate cancer. Repeat 18F-FDG PET-CT done 6 months later showed response to medical castration therapy. While the role of 18F-FDG PET-CT for sclerotic bone metastases in prostate cancer remains controversial, it appears to be useful for detection and response assessment of lytic prostate cancer metastases. (author)

  4. 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 ...

  5. Carcaça de borregos Ile de France inteiros ou castrados e Hampshire down castrados abatidos aos doze meses de idade Carcass 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

    2001-06-01

    Full Text Available Um total de 24 borregos, sendo oito Ile de France inteiros, oito Ile de France castrados e oito Hampshire Down castrados, foram utilizados com o objetivo de avaliar características qualitativas e quantitativas da carcaça. Os animais foram mantidos exclusivamente em pastagem de grama Coast-Cross, sendo abatidos aos 12 meses de idade. As carcaças provenientes de animais inteiros da raça Ile de France apresentaram significativamente maior percentagem de pescoço do que as de animais castrados da mesma raça, sendo essa a única diferença encontrada entre esses dois grupos. Porém, foram observadas diferenças na composição tecidual da paleta entre as raças, sendo que os animais da raça Ile de France (inteiros ou castrados apresentaram maior percentual de músculo e maior relação músculo/osso do que os animais da raça Hampshire Down. Os resultados indicam que, por não haver diferenças importantes entre carcaças e carnes de animais inteiros e castrados abatidos aos 12 meses de idade, o uso da castração pode ser dispensado em sistemas intensivos de produção de carne ovinaA total of 24 lambs, eight intact Ile de France, eight castrated Ile de France and eight castrated Hampshire Down, were used in this experiment with the main objective of evaluating quantitative and qualitative carcass traits. The animals were raised on a Coast-Cross pasture and slaughtered at 12 months of age. Carcasses from intact Ile de France lambs had significantly more neck than carcasses from castrated Ile de France lambs. No other differences were observed between carcasses from intact or castrated Ile de France. However, differences between breeds were observed for tissue composition of the shoulder. Shoulders from Ile de France carcasses (intact or castrated presented greater percentage of muscles and greater relation of muscles/bones than shoulders from Hampshire Down lambs. Results indicate that intact males can be recommended for sheep meat production

  6. 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

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

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    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.

  8. Prostaglandin receptor EP3 mediates growth inhibitory effect of aspirin through androgen receptor and contributes to castration resistance in prostate cancer cells.

    Science.gov (United States)

    Kashiwagi, Eiji; Shiota, Masaki; Yokomizo, Akira; Itsumi, Momoe; Inokuchi, Junichi; Uchiumi, Takeshi; Naito, Seiji

    2013-06-01

    Although numerous epidemiological studies show aspirin to reduce risk of prostate cancer, the mechanism of this effect is unclear. Here, we first confirmed that aspirin downregulated androgen receptor (AR) and prostate-specific antigen in prostate cancer cells. We also found that aspirin upregulated prostaglandin receptor subtype EP3 but not EP2 or EP4. The EP3 antagonist L798106 and EP3 knockdown increased AR expression and cell proliferation, whereas the EP3 agonist sulprostone decreased them, indicating that EP3 affects AR expression. Additionally, EP3 (PTGER3) transcript levels were significantly decreased in human prostate cancer tissues compared with those in normal human prostate tissues, suggesting that EP3 is important to prostate carcinogenesis. Decreased EP3 expression was also seen in castration-resistant subtype CxR cells compared with parental LNCaP cells. Finally, we found that aspirin and EP3 modulators affected prostate cancer cell growth. Taken together, aspirin suppressed LNCaP cell proliferation via EP3 signaling activation; EP3 downregulation contributed to prostate carcinogenesis and to progression from androgen-dependent prostate cancer to castration-resistant prostate cancer by regulating AR expression. In conclusion, cyclooxygenases and EP3 may represent attractive therapeutic molecular targets in androgen-dependent prostate cancer. PMID:23493387

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

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    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.

  10. {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

  11. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival.

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    Emma Hörnberg

    Full Text Available BACKGROUND: Constitutively active androgen receptor variants (AR-V lacking the ligand binding domain (LBD may promote the development of castration-resistant prostate cancer (CRPC. The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival. METHODOLOGY/PRINCIPAL FINDINGS: Hormone-naïve (n = 10 and CRPC bone metastases samples (n = 30 were obtained from 40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival. CONCLUSIONS/SIGNIFICANCE: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis.

  12. Circulating tumor cells in patients with metastatic castration resistant prostate cancer: exploratory findings at a tertiary referral hospital

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    Fosså SD

    2014-09-01

    Full Text Available Sophie D Fosså,1 Siri L Hess,1 Elisabeth Paus,2 Elin Borgen3 1National Resource Center for Late Effects after Cancer Treatment, 2Department of Medical Biochemistry, 3Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Radiumhospital, Oslo, Norway Objectives: In patients with metastatic castration-resistant prostate cancer (mCRPC, the finding of less than five circulating tumor cells (CTCs/7.5 mL blood before start of cytotoxic treatment or shortly thereafter indicates prolonged survival. In this descriptive pilot study, we investigated whether this association depends on the sequence of the therapeutic attempts. Patients and methods: CTCs were determined in 41 mCRPC patients before and 2–3 months after starting first-line treatment with docetaxel (group 1 or second-line treatment with either radium-223 (group 2 or placebo/best supportive care (group 3. A "favorable" CTC count was defined as <5 CTC/7.5 mL blood. The results were related to overall survival. Results: Pretreatment, six of ten men in group 1, three of 19 in group 2, and three of 12 patients in group 3 had a favorable CTC count, leading to a significant difference between first- and second-line therapy (P=0.04. Decrease of pretreatment elevated CTCs to a favorable CTC count was significantly more often observed in patients on first-line therapy (three of four patients than on second-line treatment (two of 26 men (P=0.03. A favorable CTC count before or shortly after treatment start was observed in nine of ten patients on first-line and in eight of 31 men on second-line therapy (P=0.01. A favorable CTC count pretreatment or 2–3 months after therapy start was associated with beneficial overall survival in the three groups combined and in each group analyzed separately. Conclusion: In mCRPC, a favorable CTC count before or 2–3 months after start of therapy is associated with length of overall survival, though such favorable CTC counts are observed

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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 of the...... automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide. METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate......-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...

  20. 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)

  1. Demethylation of the miR-146a promoter by 5-Aza-2’-deoxycytidine correlates with delayed progression of castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    Androgen deprivation therapy is the primary strategy for the treatment of advanced prostate cancer; however, after an initial regression, most patients will inevitably develop a fatal androgen-independent tumor. Therefore, understanding the mechanisms of the transition to androgen independence prostate cancer is critical to identify new ways to treat older patients who are ineligible for conventional chemotherapy. The effects of 5-Aza-2’-deoxycytidine (5-Aza-CdR) on the viability and the apoptosis of the androgen-dependent (LNCaP) and androgen-independent (PC3) cell lines were examined by MTS assay and western blot analysis for the activation of caspase-3. The subcutaneous LNCaP xenografts were established in a nude mice model. MiR-146a and DNMTs expressions were analyzed by qRT-PCR and DNA methylation rates of LINE-1 were measured by COBRA-IRS to determine the global DNA methylation levels. The methylation levels of miR-146a promoter region in the different groups were quantified by the bisulfite sequencing PCR (BSP) assay. We validated that 5-Aza-CdR induced cell death and increased miR-146a expression in both LNCaP and PC3 cells. Notably, the expression of miR-146a in LNCaP cells was much higher than in PC3 cells. MiR-146a inhibitor was shown to suppress apoptosis in 5-Aza-CdR-treated cells. In a castrate mouse LNCaP xenograft model, 5-Aza-CdR significantly suppressed the tumors growth and also inhibited prostate cancer progression. Meanwhile, miR-146a expression was significantly enhanced in the tumor xenografts of 5-Aza-CdR-treated mice and the androgen-dependent but not the androgen-independent stage of castrated mice. In particular, the expression of miR-146a was significantly augmented in both stages of the combined treatment (castration and 5-Aza-CdR). Additionally, the methylation percentage of the two CpG sites (−444 bp and −433 bp), which were around the NF-κB binding site at miR-146a promoter, showed the lowest methylation levels among all Cp

  2. 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

  3. A castração e seus destinos na construção da paternidade The castration and its future in paternity construction

    Directory of Open Access Journals (Sweden)

    Jacqueline de Oliveira Moreira

    2010-01-01

    Full Text Available Freud elaborou três versões sobre o pai: Édipo, o Pai da Horda e Moisés. Nessas versões o autor relata o parricídio e, portanto, para Freud, o pai é o pai morto. Se o filho é uma das soluções para a mulher, para o homem o filho assume os contornos do objeto fóbico, pois o pai se relaciona de forma privilegiada com a castração. O acesso à paternidade exige que o homem reatualize seu Édipo, colocando novamente seu desejo à prova e reativando conflitos adormecidos. Tal percurso leva, inevitavelmente, ao encontro com a castração que produz perdas narcísicas. No entanto, aqueles homens que suportam o primeiro impacto e sustentam o lugar de pai transmitem aos filhos muito mais do que genes.Freud developed three versions about the figure of the father: Oedipus, Father of the Horde, and Moses. In these versions the author reports the parricide. If the son is one of the solutions for the woman, for the man the son assumes the profile of a phobic object, because there is a privileged relationship between father and castration. The access to paternity claims that the man modernizes his Oedipus. This way takes, inevitably, to the encounter of the castration, which results in narcissistic lost. However, those men that support the first impact and sustain the father's position pass to their kids more than genes.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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

  7. 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

  8. The Evolving Biology of Castration-Resistant Prostate Cancer: Review of Recommendations From the Prostate Cancer Clinical Trials Working Group 3.

    Science.gov (United States)

    Geethakumari, Praveen Ramakrishnan; Cookson, Michael S; Kelly, William Kevin

    2016-02-01

    In 2008, the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) developed consensus guidelines for clinical trial design and conduct that redefined trial endpoints, with a dual-objective paradigm: to (1) controlling, relieving, or eliminating disease manifestations at the start of treatment; and (2) preventing or delaying further disease manifestations. Clinical and translational research in prostate cancer has expanded our current-day understanding of the mechanisms of its pathogenesis, as well as the different clinicopathologic and molecular subtypes of the disease, and has improved the therapeutic armamentarium for the management of metastatic castration-resistant prostate cancer (CRPC). These new advances led to the development of the updated PCWG3 guidelines in 2015. In this review, we analyze our evolving understanding of the biology of CRPC, acquired resistance mechanisms, and emerging therapeutic targets in light of the updated PCWG3 guidelines. We present a joint perspective from the medical oncology and urologic disciplines on the ongoing efforts to advance clinical trial performance in order to discover new therapies for this fatal disease. PMID:26888794

  9. Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research

    Science.gov (United States)

    Graff, Julie N.; Drake, Charles G.; Beer, Tomasz M.

    2016-01-01

    OBJECTIVE To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response. MATERIALS AND METHODS We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient’s response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms. RESULTS This patient’s PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T. CONCLUSION Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide. PMID:23374810

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. 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

  15. 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.

  16. A randomized phase II clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Noguchi, Masanori; Moriya, Fukuko; Koga, Noriko; Matsueda, Satoko; Sasada, Tetsuro; Yamada, Akira; Kakuma, Tatsuyuki; Itoh, Kyogo

    2016-02-01

    This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV. Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0.036 and p = 0.048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0.001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the antitumor effect of PPV, possibly due to the simultaneous decrease in Treg and increase in MDSC, in patients under PPV. PMID:26728480

  17. Progressive computed tomography (CT) appearances preceding malignant spinal cord compression (MSCC) in men with castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    Aim: To test the hypothesis that computed tomography (CT)-based signs might precede symptomatic malignant spinal cord compression (MSCC) in men with metastatic castration-resistant prostate cancer (mCRPC). Materials and methods: A database was used to identify suitable mCRPC patients. Staging CT images were retrospectively reviewed for signs preceding MSCC. Signs of malignant paravertebral fat infiltration and epidural soft-tissue disease were defined and assessed on serial CT in 34 patients with MSCC and 58 control patients. The presence and evolution of the features were summarized using descriptive statistics. Results: In MSCC patients, CT performed a median of 28 days prior to the diagnostic magnetic resonance imaging (MRI) demonstrated significant epidural soft tissue in 28 (80%) patients. The median time to MSCC from a combination of overt malignant paravertebral and epidural disease was 2.7 (0–14.6) months. Conversely, these signs were uncommon in the control cohort. Conclusions: Significant malignant paravertebral and/or epidural disease at CT precede MSCC in up to 80% of mCRPC patients and should prompt closer patient follow-up and consideration of early MRI evaluation. These CT-based features require further prospective validation. - Highlights: • MSCC is a common and devastating complication in CRPC patients. • Screening for MSCC is not performed, but men have regular staging CT scans. • We assessed CTs prior to MSCC for abnormal epidural and paravertebral signs. • Abnormal signs were visible in up to 80% of MSCC patients on prior CT scans. • Presence of these signs on CT should prompt consideration of MRI spine

  18. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  19. 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

  20. [18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments

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    Keisha C. McCall

    2015-06-01

    Full Text Available Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [18F]-fluorodeoxyglucose (FDG positron emission tomography (PET/computed tomography (CT designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer. Mice bearing LAPC4-CR subcutaneous tumors were administered [18F]-FDG via intravenous injection. After a 60-minute distribution phase, the mice were imaged on a PET/CT scanner with submillimeter resolution; and the fused PET/CT images were analyzed to evaluate tumor size, location, and metabolism across the cohort of mice. The xenograft tumors showed [18F]-FDG uptake that was independent of tumor size and was significantly greater than uptake in skeletal muscle and liver in mice (Wilcoxon signed-rank P values of .0002 and .0002, respectively. [18F]-FDG metabolism of the LAPC4-CR tumors was 2.1 ± 0.8 ID/cm3*wt, with tumor to muscle ratio of 7.4 ± 4.7 and tumor to liver background ratio of 6.7 ± 2.3. Noninvasive molecular imaging techniques such as PET/CT can be used to probe the microenvironment of tumors in vivo. This study showed that [18F]-FDG-PET/CT could be used to image and assess glucose metabolism of LAPC4-CR xenografts in vivo. Further work can investigate the use of PET/CT to quantify the metabolic response of LAPC4-CR to novel agents and combination therapies using soft tissue and possibly bone compartment xenograft models.

  1. 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

  2. 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. PMID:26710718

  3. 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

  4. 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.

  5. Effect of medical castration on CD4+ CD25+ T cells, CD8+ T cell IFN-gamma expression, and NK cells: a physiological role for testosterone and/or its metabolites.

    Science.gov (United States)

    Page, Stephanie T; Plymate, Stephen R; Bremner, William J; Matsumoto, Alvin M; Hess, David L; Lin, Daniel W; Amory, John K; Nelson, Peter S; Wu, Jennifer D

    2006-05-01

    The higher prevalence of autoimmune disease among women compared with men suggests that steroids impact immune regulation. To investigate how sex steroids modulate cellular immune function, we conducted a randomized trial in 12 healthy men aged 35-55 yr treated for 28 days with placebo, a GnRH antagonist, acyline to induce medical castration, or acyline plus daily testosterone (T) gel to replace serum T, followed by a 28-day recovery period. Serum hormones were measured weekly and peripheral blood lymphocytes (PBLs) were collected biweekly for analyses of thymus-derived lymphocyte (T cell) subtypes and natural killer (NK) cells. Compared with the other groups and to baseline throughout the drug exposure period, men receiving acyline alone had significant reductions in serum T (near or below castrate levels), dihydrotestosterone, and estradiol (P physiological balance of autoimmunity and protective immunity by preserving the number of regulatory T cells and the activation of CD8+ T cells. In addition, sex steroids suppress NK cell proliferation. This study supports a complex physiological role for T and/or its metabolites in immune regulation. PMID:16352669

  6. Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network.

    Science.gov (United States)

    Zhu, Jin; Wang, Sugui; Zhang, Wenyu; Qiu, Junyi; Shan, Yuxi; Yang, Dongrong; Shen, Bairong

    2015-12-22

    High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4-2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development. PMID:26540468

  7. 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

  8. {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

  9. 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

  10. 18F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

    International Nuclear Information System (INIS)

    We investigated the role of 18F-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 to

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

    Science.gov (United States)

    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-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response (≥50% decline), and time to skeletal-related event. Results Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02–2.24) for centrally assessed rPFS, 0.77 (0.28–2.15) for OS, 0.21 (0.08–0.51) for time to chemotherapy, and 0.31 (0.17–0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade ≥3 occurred in 33% of enzalutamide-treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97–1.10). Conclusions In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991). PMID:27195316

  12. 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.

  13. 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。

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

    Directory of Open Access Journals (Sweden)

    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

  15. Efficacy and safety of second-line agents for treatment of metastatic castration-resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Gianpaolo Perletti

    2015-07-01

    Full Text Available Objective: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel. Materials and Methods: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS and severe adverse effects (grade 3 or higher. Results: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebotreated, the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001, 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001 and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001. Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001. Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects

  16. Can palliative radiotherapy influence prostate-specific antigen response in patients with castrate-resistant prostate cancer treated with systemic therapy (chemotherapy or abiraterone)?—a report of three cases

    International Nuclear Information System (INIS)

    Palliative radiotherapy (pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer (CRPC). However, evidence that pRT influences prostate-specific antigen response in patients with CRPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel (n=2) and abiraterone (n=1), who responded unusually after pRT for bone pain with the development of a significant biochemical response and restoration of response to systemic therapy. The possibility of pRT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment

  17. 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

  18. 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

    Directory of Open Access Journals (Sweden)

    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

  19. 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

  20. 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.)

  1. 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

  2. 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

  3. 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 .

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Comparative therapeutic use of Risedronate and Calcarea phosphorica - allopathy versus homeopathy - in bone repair in castrated rats Comparação do uso terapêutico de Risedronato e Calcarea phosphorica - alopatia versus homeopatia - no reparo ósseo em ratos castrados

    Directory of Open Access Journals (Sweden)

    Cristina Werkman

    2006-09-01

    Full Text Available Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies in the past few years. It results in a much higher risk for fractures and might cause slower bone lesion healing. The aim of this work was to study the effects of Risedronate (allopathic medicine and Calcarea phosphorica 6CH (homeopathic medicine on the repair of bone lesions in male rats with osteoporosis induced by castration. Eighty-four three-month-old rats were used divided into four groups of twenty-one animals each. Three groups where castrated and one group was submitted to Sham surgery. One month later, cortical lesions were made in all animals' tibiae and, after one day, the different experimental treatments began according to the following groups: CR - castrated/Risedronate (1 mg/kg/day; CCp - castrated/Calcarea phosphorica 6CH (3 drops/day; CP - castrated/placebo and SP - Sham/placebo. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of the treatments and had their tibiae removed. Digital radiographs of the tibiae were taken and analyzed in order to evaluate the optical density of the defect area. Then, they were decalcified and processed for histological and histomorphometrical analysis. The data were submitted to ANOVA, and to the Tukey and Dunnett tests (5%. The allopathic and homeopathic treatments led to different bone formation as regards remodeling and maturation aspects. Further research is necessary to access the resistance and quality of the newly formed bone.A osteoporose, doença caracterizada pela perda de massa óssea, tem sido alvo de estudos nos últimos anos. Fraturas decorrentes da osteoporose são muito comuns e podem apresentar consolidação mais lenta. O objetivo deste trabalho foi avaliar o efeito do risedronato (medicamento alopático e da Calcarea phosphorica 6CH (medicamento homeopático no reparo de lesões ósseas em ratos com osteoporose induzida por castra

  10. 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

  11. 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)

  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. 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);

  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. Desenvolvimento ponderal de bovinos de corte de diferentes grupos genéticos de Charolês x Nelore inteiros ou castrados aos oito meses Growth of beef cattle from different genetic groups of Charolais x Nellore intact or castrated at eight months

    Directory of Open Access Journals (Sweden)

    Lígia Pigatto Pereira

    2000-12-01

    Full Text Available O objetivo deste trabalho foi avaliar animais inteiros ou castrados aos oito meses, de diferentes sistemas de acasalamento (SA: de raça definida (D, cruzados da primeira (G1 e da segunda (G2 geração, e de diferentes grupos genéticos (GG em cada SA, D: Charolês (C vs Nelore (N, G1: ½CN vs ½NC e G2: ¾CN vs ¾NC, quanto ao desenvolvimento ponderal desde o nascimento até o abate. Foram utilizados 78 animais desmamados aos três meses, confinados dos 7 aos 12 meses (primeiro inverno/primavera, mantidos em pastagem natural (PN dos 12 aos 20 meses (segundo verão/outono e confinados dos 20 aos 24 meses (segundo inverno/primavera, quando foram abatidos. Foi observada heterose de 20,44% para G1 e 14,44% para G2 no peso aos 24 meses. Entre os definidos, o C foi mais pesado que o N em todas as idades avaliadas. Na G2, ocorreram diferenças em peso (PThe objective of this work was to evaluate the growth of beef cattle intact or castrated at eight months, from different mating systems (MS: straightbreds (S, crossbreds of first (G1 and second (G2 generation, and of different genetic groups (GG in each MS, S: Charolais (C vs Nellore (N, G1: ½CN vs ½NC and G2: ¾CN vs ¾NC. Seventy-eight animals, weaned at three months, were submitted to feedlot from 7 to 12 months (first winter/spring, maintained in native pasture (NP from 12 to 20 months (second summer/autumn, and finished in feedlot from 20 to 2 4 months (second winter/spring, when they were slaughtered. Heterosis of 20.44% for G1 and 14.44% for G2 was observed for weight at 24 months. The C was heavier than the N in all ages. In the G2, the ¾CN was heavier (P<.05 at three, eight and twelve months. Intact animals presented higher (P<.05 ADG than the castrated ones during the first feedlot period, but in NP no difference occurred between sexual condition. Heterosis for weight per day of age was 22.25% for G1 and 14.54% for G2. The G2 animals had lower ADG than the S and G1 during the first feedlot

  19. 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

  20. 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

  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. 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

  3. [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

  4. 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

  5. Desempenho e características da carcaça e da carne de novilhos não-castrados alimentados com ou sem adição de monensina e/ou probiótico à dieta Performance, carcass and meat traits of non-castrated cattle fed with or without monensin and/or probiotic addition to the diet

    Directory of Open Access Journals (Sweden)

    Fernando Kuss

    2009-07-01

    Full Text Available O objetivo do estudo foi avaliar o desempenho e as características da carcaça e da carne de novilhos não-castrados alimentados com ou sem adição de monensina (M e/ou probiótico (P (Sacharomyces cerevisiae à dieta. Os animais foram distribuídos em baias individuais, permanecendo 145 dias em confinamento. A dieta foi composta de silagem de milho e 1,2% do peso vivo de concentrado com base da matéria natural. Não houve efeito da adição dos aditivos fornecidos de forma isolada ou mesmo da associação destes sobre o consumo de alimento, o ganho de peso e a conversão alimentar. As médias de consumo, ganho de peso e conversão alimentar apresentaram comportamento quadrático com o avanço do período de confinamento. Embora a adição de M ou P à dieta tenha resultado no aumento numérico (P>0,05 do consumo (4,2%, a média de ganho de peso reduziu (5,8 e 5,3%, respectivamente, resultando em pior conversão alimentar (P>0,05. Já a associação de M+P aumentou (P>0,05 o consumo em 9,5%, com concomitante aumento (P>0,05 do ganho de peso (6,4% em relação à dieta controle. Os animais alimentados com M+P apresentaram melhor acabamento de carcaça (5,5mm, seguidos por aqueles do grupo controle (4,7mm, sendo os valores inferiores verificados nas carcaças dos animais M (3,7mm e P (3,5mm. A adição de monensina e/ou probiótico (Sacharomyces cerevisiae na dieta de novilhos na fase de terminação em confinamento não proporciona melhora no desempenho e nas características da carcaça e da carne de novilhos.The objective of this experiment was to evaluate the performance, carcass and meat characteristics of non-castrated cattle with or without monensin (M and/or probiotic (P (Saccharomyces cerevisiae to the diet. The animals were divided into individual stalls, being left 145 days in feedlot. The roughage used was corn silage + 1.2% of the weight live of concentrate in natural matter basis. There was no effect of the addition of the

  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. 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

    BACKGROUND: The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial. OBJECTIVE: To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone. DESIGN, SETTING, AND PARTIC...

  10. 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.

  11. 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.

  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. 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

  14. 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...

  15. [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

  16. 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...

  17. 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...

  18. 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...

  19. 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

  20. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Janet E. Brown

    2010-09-01

    Full Text Available 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 affecting PSA levels. As bone metastases develop, factors derived from bone metabolism are released into blood and urine, including N- and C-terminal peptide fragments of type 1 collagen and bone-specific alkaline phosphatase, which represent potentially useful biomarkers for monitoring metastatic bone disease. A number of clinical trials have investigated these bone biomarkers with respect to their diagnostic, prognostic, and predictive values. Results suggest that higher levels of bone biomarkers are associated with an increased risk of skeletal-related events and/or death. As a result of these findings, bone biomarkers are now being increasingly used as study end points, particularly in studies investigating novel agents with putative bone effects. Data from prospective clinical trials are needed to validate the use of bone biomarkers and to confirm that marker levels provide additional information beyond traditional methods of response evaluation for patients with metastatic prostate cancer.

  1. 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...

  2. [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

  3. Castration Has Antihypertensive and Organoprotective Effects in Male but Not in Female Heterozygous Ren-2 Rats

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Husková, Z.; Vaňourková, Z.; Červenka, L.

    2011-01-01

    Roč. 34, č. 1 (2011), s. 46-52. ISSN 1420-4096 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : Ren-2 rats * hypertension * sexual dimorphism * age * sex hormones * renin-angiotensin system Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.464, year: 2011

  4. "Gold Is Every Man's Opportunity": Castration Anxiety and the Economic Venture in "Deadwood"

    Science.gov (United States)

    Wiggins, Kyle; Holmberg, David

    2007-01-01

    David Milch, creator of HBO's critically acclaimed Western series, "Deadwood," said, "The only reason the town of Deadwood exists is gold." Milch bluntly discards the Western genre's foundational ideology of self-determination, considering these principles a delusion that obscures the material realities of the late nineteenth century. Were it not…

  5. 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 ...

  6. "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…

  7. 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.

  8. 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...

  9. 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

    were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade ≥3 sensory neuropathy, nail disorders and asthenia/fatigue. CONCLUSIONS: Docetaxel rechallenge is a management option for responders to docetaxel with a PFI of >6 months, but did not prolong survival. Potential...

  10. 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

  11. 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. PMID:26760770

  12. BAY 1024767 blocks androgen receptor mutants found in castration-resistant prostate cancer patients

    OpenAIRE

    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

    2016-01-01

    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...

  13. 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...

  14. 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...

  15. 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

  16. A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform.

    Science.gov (United States)

    Deeken, J F; Cormier, T; Price, D K; Sissung, T M; Steinberg, S M; Tran, K; Liewehr, D J; Dahut, W L; Miao, X; Figg, W D

    2010-06-01

    The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide. PMID:20038957

  17. 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%, P<0.001) and grade 3 nonhematological toxicity (56% vs. 43%, P = 0.022). Patients treated with D alone were also more frequently hospitalized (53% vs. 41%, P = 0.035), mainly owing to a higher incidence of febrile neutropenia in this group (25% vs. 10%, P<0......% 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...

  18. 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...

  19. 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

  20. Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

    Science.gov (United States)

    Goh, H H; Chew, P C; Karim, S M; Ratnam, S S

    1980-02-01

    Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH. PMID:6772356

  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

    /d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. RESULTS: Overall, 873 patients were randomly assigned to receive sunitinib (n...

  2. 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

  3. 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

  4. 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

    .6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P ...BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years...

  5. 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

  6. 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

  7. 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...

  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. Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, Chris J; Iversen, Peter; Tammela, Teuvo; Anderson, John; Björk, Thomas; Kaisary, Amir V; Morris, Thomas

    2006-01-01

    To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint.......To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint....

  10. 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

  11. Carcaça de borregos Ile de France inteiros ou castrados e Hampshire down castrados abatidos aos doze meses de idade Carcass of intact or castrated Ile de France and castrated Hampshire down lambs slaughtered at twelve months of age

    OpenAIRE

    Edson Luis de Azambuja Ribeiro; Marco Antônio da Rocha; Ivone Yurika Mizubuti; Leandro das Dores Ferreira da Silva; Horaci Jaqueline Silva de Souza Ribeiro; Rinaldo Masato Mori

    2001-01-01

    Um total de 24 borregos, sendo oito Ile de France inteiros, oito Ile de France castrados e oito Hampshire Down castrados, foram utilizados com o objetivo de avaliar características qualitativas e quantitativas da carcaça. Os animais foram mantidos exclusivamente em pastagem de grama Coast-Cross, sendo abatidos aos 12 meses de idade. As carcaças provenientes de animais inteiros da raça Ile de France apresentaram significativamente maior percentagem de pescoço do que as de animais castrados da ...

  12. 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.

  13. Alternativen zur betäubungslosen Ferkelkastration: Verbraucherakzeptanz

    OpenAIRE

    Heid, Astrid; Hamm, Ulrich

    2011-01-01

    In organic farming there is an ongoing discussion on piglet castration without anaesthesia and possible alternatives to this practice due to animal welfare concerns. Consumer acceptance of alternatives to piglet castration without anaesthesia plays an important role in this discussion. This contribution examines organic consumers’ attitudes towards piglet castration without anaesthesia and the alternatives castration with anaesthesia and analgesia, immunocastration and fattening of entire mal...

  14. Untersuchungen zur Wirksamkeit und Gewebeverträglichkeit von Lokalanästhetika bei der Kastration männlicher Saugferkel

    OpenAIRE

    Zankl, Anke

    2007-01-01

    Analysis of efficacy and tissue tolerance of local anaesthetics administered prior to castration of male suckling piglets Objective of this project was to examine the efficacy and tissue tolerance of various local anaesthetics used in castration of male suckling piglets. Four to six days old healthy animals were randomized into trial groups (I to IX). Animals of the control groups (I to IV) were treated analogous to the castration groups (V to IX) but not castrated. In groups "Handlin...

  15. 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.)

  16. 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

    endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. FINDINGS: From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the......%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. INTERPRETATION: Although there was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that...

  17. 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

    OpenAIRE

    Luiza Vieira Couto; Wilson Camilo Chaves

    2009-01-01

    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...

  18. 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.

  19. 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...

  20. Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    177Lu-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 177Lu-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 177Lu-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 177Lu-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.)

  1. 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.

  2. 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...

  3. 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...

  4. 21 CFR 522.1367 - Meloxicam.

    Science.gov (United States)

    2010-04-01

    ...) Indications for use. For the control of postoperative pain and inflammation associated with orthopedic surgery, ovariohysterectomy, and castration when administered prior to surgery. (iii) Limitations. Federal law restricts...

  5. 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.

  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...

  7. 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 to...

  8. 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.

  9. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P; Christensen, I; Denis, L

    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...

  10. The Effect of Immunocastration on Some Meat Quality Characteristics

    Directory of Open Access Journals (Sweden)

    Ioana Andronie

    2015-05-01

    Full Text Available Surgical castration of male pigs has become increasingly less accepted at present due to the fact that it is a direct animal welfare concern. UE welfare conditions demand that this method be dropped starting 2018 in order to eliminate the stress and associated pain it induces. Immunocastration is one of the alternatives to surgical castration that ensures male pig welfare and eliminates the boar smell of the meat. The objective of this research has been to identify the immunocastration effects on meat quality, compared with the meat from surgically castrated pigs. The animals assessed during research were fattening PIC pigs, grouped into two lots: surgically castrated pigs (SC and immunocastrated pigs (IC. Pig immunization was achieved by means of ImprovacTM. The results have shown that immunocastrated pigs recorded a 60.2% carcass meat compared to the 59.69% carcass meat achieved in surgically castrated pigs, thus displaying statistically insignificant differences (p≥0.05. Fat layer thickness was significantly lower in immunocastrated pigs compared to the marker lot (p≤0.05. Mycoplasma hyopneumoniae lung lesions recorded were lower in immunocastrated pigs compared to the surgically castrated animals (p≥0.05. Despite the fact that differences have been statistically insignificant, we are able to confirm that immunocastrated pigs display a lower incidence of respiratory disease compared to surgically castrated pigs.  In this study there were not significant differences in meat quality between surgically castrated pigs and immunocastrated pigs.

  11. Comparison of prostate gene expression and tissue weight changes as monitors of antiandrogen activity in GNRH-inhibited rats

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Lefevre, P. A.; Ashby, J.

    2003-01-01

    BACKGROUND: The Hershberger assay for antiandrogens and modifiers of steroid biosynthesis uses surgically-castrated rats. We described an adaptation of the assay using the GnRH inhibitor Antarelix in place of surgical castration [Ashby J, Lefevre PA, Deghenghi R, Wallis N. Regulatory Toxicology a...

  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 in...... peripubertal male rabbits (SG; n=10), as a mean of hormonal castration. Blood samples (for testosterone measurements), body weight and testicular volume were taken on days (D) 0, 14 and 90. Surgical castration was performed on D90 for testicular histology. Age-matched animals following the same protocol...

  13. Desempenho e características da carcaça e da carne de novilhos não-castrados alimentados com ou sem adição de monensina e/ou probiótico à dieta Performance, carcass and meat traits of non-castrated cattle fed with or without monensin and/or probiotic addition to the diet

    OpenAIRE

    Fernando Kuss; José Luis Moletta; Meiby Carneiro de Paula; Ivan César Furmann Moura; Stefano Juliano Tavares de Andrade; André Guimarães Maciel e Silva

    2009-01-01

    O objetivo do estudo foi avaliar o desempenho e as características da carcaça e da carne de novilhos não-castrados alimentados com ou sem adição de monensina (M) e/ou probiótico (P) (Sacharomyces cerevisiae) à dieta. Os animais foram distribuídos em baias individuais, permanecendo 145 dias em confinamento. A dieta foi composta de silagem de milho e 1,2% do peso vivo de concentrado com base da matéria natural. Não houve efeito da adição dos aditivos fornecidos de forma isolada ou mesmo da asso...

  14. 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.

  15. 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.

  16. 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

    OpenAIRE

    Eloiza Lanferdini; Paulo Alberto Lovatto; Raquel Melchior; Cristieli Carolina Klein; Jomara Broch; Gerson Guarez Garcia

    2012-01-01

    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 aliment...

  17. 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)

    OpenAIRE

    Rony Antonio Ferreira; Rita Flávia Miranda de Oliveira; Juarez Lopes Donzele; Darci Clementino Lopes; Uislei Antonio Dias Orlando; Wilkson de Oliveira Resende; Roberta Gomes Marçal Vieira Vaz

    2003-01-01

    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 ra...

  18. Exigência de Lisina para Machos Castrados de Dois Grupos Genéticos de Suínos na Fase de Terminação, com Base no Conceito de Proteína Ideal Lysine Requirement for Castrated Males of Two Genetic Groups of Swine During Finishing Phase, Based on the Ideal Protein Concept

    OpenAIRE

    Ivan Moreira; Luiz Fernando Gasparotto; Antônio Cláudio Furlan; Valquíria Mayumi Ishida Patrício; Gisele Cristina de Oliveira

    2002-01-01

    Foi conduzido um experimento para determinar as exigências de lisina de machos castrados, em fase de terminação, de dois grupos genéticos de suínos, com base no conceito de proteína ideal. Foram utilizados 16 suínos do grupo genético comum (GGC) e 16 suínos do grupo genético melhorado (GGM), distribuídos em quatro tratamentos que consistiram de uma ração basal, à base de milho e farelo de soja, contendo 0,60% de lisina e outras três rações, acrescentando-se níveis crescentes de lisina para se...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Influence de la castration précoce et de la restriction alimentaire sur les caractéristiques du collagène intramusculaire et sur la texture de la viande chez le bovin mâle en croissance

    OpenAIRE

    Damergi, C.; Geay, Y; Picard, B.; Lepetit, J.; JAILLER, R.; Canistro, J.

    1995-01-01

    Les propriétés mécaniques du tissu conjonctif intramusculaire ainsi que son degré de rétraction au cours du chauffage jouent un rôle déterminant sur la tendreté de la viande cuite. En effet, la dénaturation du collagène fibrillaire s’accompagne d’une contraction plus ou moins importante selon sa stabilité thermique. Cependant, les relations entre les caractéristiques biochimiques du collagène et les propriétés mécaniques du tissu conjonctif intramusculaire ne sont pas encore bien élucidées. L...

  4. 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...

  5. 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....

  6. 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

    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......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...

  7. [Testosterone and Induced Humoral Immunity in Male Campbell Dwarf Hamsters (Phodopus campbelli, Thomas, 1905, Rodentia, Cricetidae): Experimental Manipulation of Testosterone Levels].

    Science.gov (United States)

    Vasilieva, N Yu; Khrushchova, A M; Shekarova, N; Rogovin, K A

    2015-01-01

    In this paper we report the results of testosterone manipulation in the blood of male Campbell dwarf hamsters Phodopus campbelli Thomas, 1905 through castration, followed by testosterone treatment. Under these conditions, we studied antibody production rates in response to injection with sheep red blood cells (SRBC). It was shown that castration induced a dramatic decrease in blood testosterone but had no effect on the humoral response to SRBC. Males that received a testosterone compound with a long-lasting action (omnadren) exhibited a poor response to SRBC following re-exposure in the context of elevated testosterone compared to castrated males inoculated with an oil base of the drug. PMID:26349233

  8. 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...... 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...

  9. [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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

    OpenAIRE

    Zhang, Xinhua; Zang, Ning; Wei, Yu; Yin, Jin; Teng, Ruobing; Seftel, Allen; DiSanto, Michael E.

    2011-01-01

    Testosterone (T) plays a permissive role in the development of benign prostatic hyperplasia (BPH), and phosphodiesterase 5 inhibitors (PDE5is) have been found to be effective for BPH and lower urinary tract symptoms (LUTS) in clinical trials. This study investigated the effect of T on smooth muscle (SM) contractile and regulatory signaling pathways, including PDE5 expression and functional activity in prostate in male rats (sham-operated, surgically castrated, and castrated with T supplementa...

  17. Lack of Direct Androgen Regulation of PDE5 Expression

    OpenAIRE

    Yang, Rong; Huang, Yun-Ching; Lin, Guiting; Wang, Guifang; Hung, Steven; Dai, Yu-Tian; Sun, Ze-Yu; Lue, Tom F.; Lin, Ching-Shwun

    2009-01-01

    It has been reported that penile PDE5 expression was under androgen regulation. However it remained unknown whether the observed change in PDE5 expression in castrated animals was under direct androgen regulation or due to changes in smooth muscle content. In the present study we showed that castration of rats caused a reduction of penile size and cavernous smooth muscle content. Immunostaining detected concomitant reduction of PDE5 and alpha smooth muscle actin (α-SMA) expression in the corp...

  18. Ractopamine in diets for finishing pigs of different sexual categories

    OpenAIRE

    Carlos Enrique da Trindade Barbosa; Carolina Teixeira Costa Silva; Vinícius de Souza Cantarelli; Márcio Gilberto Zangeronimo; Raimundo Vicente de Sousa; Cesar Augusto Pospissil Garbossa; Níkolas de Oliveira Amaral; Walmes Marques Zeviani

    2012-01-01

    Performance and carcass and cut yield of finishing pigs of three sexual categories fed diets with different levels of ractopamine were studied. Forty-eight hybrid animals (initial weight of 92.1±2.4 kg) were distributed in a completely randomised design in 3 × 2 factorial arrangement (three sexual categories: surgically castrated males, two females and immunologically castrated males - with or without 10 ppm of ractopamine), totalling six treatments and eight repetitions with one animal per e...

  19. 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...

  20. 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...

  1. 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...

  2. The Effect of Immunocastration on Some Meat Quality Characteristics

    OpenAIRE

    Ioana Andronie

    2015-01-01

    Surgical castration of male pigs has become increasingly less accepted at present due to the fact that it is a direct animal welfare concern. UE welfare conditions demand that this method be dropped starting 2018 in order to eliminate the stress and associated pain it induces. Immunocastration is one of the alternatives to surgical castration that ensures male pig welfare and eliminates the boar smell of the meat. The objective of this research has been to identify the immunocastration effect...

  3. Development, validation and application of a stable isotope dilution liquid chromatography electrospray ionization/selected reaction monitoring/mass spectrometry (SID-LC/ESI/SRM/MS) method for quantification of keto-androgens in human serum✩, ✩✩

    OpenAIRE

    Tamae, Daniel; Byrns, Michael; Marck, Brett; Mostaghel, Elahe A.; Peter S Nelson; de Lange, Paul; Lin, Daniel; Taplin, Mary-Ellen; Balk, Steven; Ellis, William; True, Larry; Vessella, Robert; Montgomery, Bruce; Blair, Ian A.; Penning, Trevor M.

    2013-01-01

    Prostate cancer is the most frequently diagnosed form of cancer in males in the United States. The disease is androgen driven and the use of orchiectomy or chemical castration, known as androgen deprivation therapy (ADT) has been employed for the treatment of advanced prostate cancer for over 70 years. Agents such as GnRH agonists and non-steroidal androgen receptor antagonists are routinely used in the clinic, but eventually relapse occurs due to the emergence of castration-resistant prostat...

  4. Postcastration eventration in 18 horses: the prognostic indicators for long-term survival (1985-1995).

    OpenAIRE

    Thomas, H. L.; Zaruby, J F; Smith, C. L.; Livesey, M A

    1998-01-01

    Castration of horses is considered a common and routine surgical procedure, but the potential for complications is high. By far the most serious of these is eventration. The objectives of this study were to determine the long-term survival of horses undergoing surgical treatment of indirect (1) inguinal eventration of the small intestine following castration, and to identify prognostic indicators for survival. The case records of 18 horses undergoing surgical treatment of postcastration event...

  5. 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...

  6. 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) ...

  7. [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

  8. 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

  9. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    International Nuclear Information System (INIS)

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion

  10. 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

  11. 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.

  12. Redução da proteína bruta da ração e suplementação de aminoácidos para suínos machos castrados dos 15 aos 30 kg mantidos em ambiente de alta temperatura Effect of feeding reduced crude protein, amino acid-supplemented diets on performance of castrated swine from 15 to 30 kg on high environmental temperature

    OpenAIRE

    Rony Antonio Ferreira; Rita Flávia Miranda de Oliveira; Juarez Lopes Donzele; Cláudio Vieira de Araújo; Francisco Carlos de Oliveira Silva; Roberta Gomes Marçal Vieira Vaz; Wilkson Oliveira Rezende

    2006-01-01

    Um experimento foi conduzido para avaliar a influência da redução da proteína bruta (PB) e da suplementação de aminoácidos sintéticos em rações sobre o desempenho de suínos machos castrados mantidos em ambiente de alta temperatura (32ºC). Foram utilizados 60 leitões mestiços (Landrace x Large White) com peso médio inicial de 15,2 kg, distribuídos em um delineamento inteiramente ao acaso, com cinco tratamentos (18, 17, 16, 15 e 14% de PB), seis repetições e dois animais por unidade experimenta...

  13. [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

  14. Genotypic variation in host response to infection affects parasite reproductive rate.

    Science.gov (United States)

    Tavalire, Hannah F; Blouin, Michael S; Steinauer, Michelle L

    2016-02-01

    Parasite fitness is largely influenced by a variation in host response due to the host's genetic background. Here we investigated the impact of host genotype on pathogen success in the snail vector of its castrating parasite, Schistosoma mansoni. We infected five inbred lines of Biomphalaria glabrata with two infection doses and followed their growth, reproductive output and parasite production throughout the course of infection. There was no difference in resistance to infection among inbred lines, but lines varied in their responses to infection and the numbers of parasites produced. Snails did not compensate for castration by increasing their fecundity during the early phase of infection (fecundity compensation). However, some lines were able to delay parasite shedding for up to 30 weeks, thus prolonging reproduction before the onset of castration. Here we propose this strategy as a novel defense against castrating pathogens in snails. Gigantism, a predicted outcome of castration due to energy reallocation, occurred early in infection (cercariae within a single 2h shedding period, resulting in a total production of 6981-29,509 cercariae over the lifetime of a single snail. Regardless of genetic background, snail size was a strong predictor of parasite reproduction: each millimetre increase in snail size at the time of the first shed resulted in up to 3500 more cercariae over the lifetime of the snail. The results of this study provide a detailed picture of variation in hosts' responses to infection and the resulting impacts on parasite fitness, further defining the intricacies of snail-schistosome compatibility. PMID:26552016

  15. 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.

  16. 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

  17. 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

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

    Science.gov (United States)

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

    2014-12-01

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

  19. 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...

  20. 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.

  1. Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per Zier;

    2013-01-01

    studies that exclusively enrolled patients with CRPC receiving androgen deprivation therapy (ie, testosterone (T) levels #50 ng/dL), this phase II study assessed the efficacy and safety of ENZA monotherapy in patients who had never received hormone therapy; presenting with non-castrate T levels ($230 ng....../dL). Methods: This was a 25-wk, open-label, single-arm study of patients with hormone-naïve, histologically confirmed prostate cancer (all stages) requiring hormonal treatment, an ECOG PS score of 0,and a life expectancy .1 y. All patients received ENZA 160 mg/d without concomitment castration. Primary endpoint......Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor that has been approved in the US and shown to increase overall survival by 4.8 months over a placebo (HR,0.63) in patients with metastatic castration resistant prostate cancer (CRPC) previously treated with docetaxel (Scher et...

  2. 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

  3. 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

  4. Risk of Hormone Escape in a Human Prostate Cancer Model Depends on Therapy Modalities and Can Be Reduced by Tyrosine Kinase Inhibitors

    Science.gov (United States)

    Guyader, Charlotte; Céraline, Jocelyn; Gravier, Eléonore; Morin, Aurélie; Michel, Sandrine; Erdmann, Eva; de Pinieux, Gonzague; Cabon, Florence; Bergerat, Jean-Pierre; Poupon, Marie-France; Oudard, Stéphane

    2012-01-01

    Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape -frequency and delay- are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH) antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR) antagonists (bicalutamide or flutamide). Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration), but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR) as compared to continuous castration (RRintermittent: 14.5, RRcomplete blockade: 6.5 and 1.35). All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17) and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent tumors displayed

  5. 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.

  6. Analysis of pain-related vocalization in young pigs

    Science.gov (United States)

    Marx, G.; Horn, T.; Thielebein, J.; Knubel, B.; von Borell, E.

    2003-09-01

    The assessment of pain constitutes a major issue for animal welfare research. The objective of this study was to classify vocalizations during castration pain and to assess alterations in vocalizations under local anaesthesia. The alterations in vocalization were measured by multiparametric call analysis. A total of 4537 calls of 70 young pigs were evaluated. With the data of this study three call types are distinguishable (grunt, squeal, scream). A high percentage (94.64%) of calls that could be classified in one of the three call types during the castration process within the confidence level of 95% was found. The comparison of the occurrence of the call types during treatments gives evidence for pain-related use of screams. The piglets castrated without local anaesthesia produced almost double the number of screams as piglets castrated with anaesthesia. The comparison of the recorded sound parameters reveals the particular position of screams in the call repertoire of young pigs. Screams are significantly different in their sound parameters than grunts or squeals. Castration in comparison to mere restraint produced a comprehensive change in sound parameters, with castration calls becoming more extended and more powerful. The findings in this study also show differences in the effectiveness of the parameters which indicate pain. Parameters that describe a single event in a call, such as peak level or peak frequency give better results than parameters that describe an average, such as weighted frequency and main frequency. The research indicated that pain-related changes of calls in piglets can be identified. On the basis of the results, automatic classification of call types during management operations may be developed. This could contribute to objective animal welfare assessment.

  7. 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.

  8. 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

  9. 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...

  10. Management of patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Gillessen, S; Omlin, A; Attard, G;

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration......-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not...

  11. La demande transsexuelle : quels mécanismes ?

    OpenAIRE

    Mormont, Christian; Michel, Aude

    1996-01-01

    We may suppose that, in first phase, the transsexual, submitted to fear of castration, could not master it and thus finds himself always yielding to it. To end this apprehension, it will confront it actively by asking for the ablation of his/her genitals. The second step is to convert this performed castration by acquisition of an organ "in place" and not only "instead of", as an active conquest in comparison with the very only lack of penis. The counter-pbobic hypothesis does not pretend to ...

  12. 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

  13. Welfare of entire males and females in organic pig production when reared in single-sex groups

    DEFF Research Database (Denmark)

    Thomsen, Rikke; Bonde, Marianne Kjær; Rousing, Tine;

    2012-01-01

    In the 25 EU countries more than 100 million male piglets are castrated each year. Castration is particularly problematic in organic pig production because it conflicts with the high welfare and other ethical standards associated with this system of animal production. The objective was to...... investigate possible welfare implications of producing organic entire male pigs. A total of 281 entire male pigs and 250 female pigs, raised in accordance with Danish organic standards in two commercial herds, were distributed into 15 male groups and 15 female groups. The pigs were observed at 40, 70 and 90...

  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. 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

  16. 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

  17. 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

  18. 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...

  19. 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

  20. The Benefits of Neutering Cats and Dogs: A Conversation

    Science.gov (United States)

    The castration of a dog or cat can be an emotion laden issue. In many cases it is the best solution for resolving behavior related problems as well as an important method for decreasing pet overpopulation. Sometimes the idea is met with resistance, particularly by some male owner...

  1. Prostate cancer stem cells: The case for model systems

    Directory of Open Access Journals (Sweden)

    Paul G Hynes

    2012-01-01

    Full Text Available Advanced prostate cancers are treated with androgen deprivation therapy, which usually leads to a rapid and significant reduction in tumor burden but subsequent development of castration-resistant and metastatic disease almost always occurs. The source of tumor heterogeneity and the accompanying mechanisms leading to treatment resistance are major areas of prostate cancer research. Although our understanding of tumor heterogeneity is evolving, the functional isolation of tumor propagating populations, also known as cancer stem cells (CSCs, is fundamental to the identification and molecular characterization of castration-resistant prostate cancer cells. Of clinical importance, knowledge of prostate CSCs has implications for design of next generation-targeted therapies aimed at both eradicating primary tumor mass and preventing castration-resistant disease. The inability to routinely transplant fractionated primary human prostate tumors has prevented progress in analyzing the source of heterogeneous and treatment-resistant populations in prostate cancer. Here, we briefly overview the mechanisms of castration resistance, including the hypothesis for the existence of androgen-independent prostate CSCs. Finally, we discuss the interpretation of preclinical models and their utility for characterizing prostate CSCs in androgen-replete and androgen-deprived conditions.

  2. 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

  3. 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.

  4. 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

  5. Atrial septal defect in a ferret

    NARCIS (Netherlands)

    van Schaik-Gerritsen, K.M.; Schoemaker, N.J.; Kik, M.J.L.; Beijerink, N.J.

    2013-01-01

    Abstract A 2-year-old, male castrated ferret (Mustela putorius furo) was presented with progressive abdominal distention and loss of muscle mass despite normal appetite. Physical examination findings included pale mucous membranes, a prolonged capillary refill time, a pulse rate greater than 300 bea

  6. GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer.

    Science.gov (United States)

    Labrie, Fernand

    2014-08-01

    The discovery of medical castration with GnRH agonists in 1979 rapidly replaced surgical castration and high doses of estrogens for the treatment of prostate cancer. Soon afterwards, it was discovered that androgens were made locally in the prostate from the inactive precursor DHEA of adrenal origin, a mechanism called intracrinology. Taking into account these novel facts, combined androgen blockade (CAB) using a pure antiandrogen combined with castration in order to block the two sources of androgens was first published in 1982. CAB was the first treatment shown in randomized and placebo-controlled trials to prolong life in prostate cancer, even at the metastatic stage. Most importantly, the results recently obtained with the novel pure antiandrogen enzalutamide as well as with abiraterone, an inhibitor of 17α-hydroxylase in castration-resistant prostate cancer, has revitalized the CAB concept. The effects of CAB observed on survival of heavily pretreated patients further demonstrates the importance of the androgens made locally in the prostate and are a strong motivation to apply CAB to efficiently block all sources of androgens earlier at start of treatment and, even better, before metastasis occurs. The future of research in this field thus seems to be centered on the development of more potent blockers of androgens formation and action in order to obtain better results at the metastatic stage and, for the localized stage, reduce the duration of treatment required to achieve complete apoptosis and control of prostate cancer proliferation before it reaches the metastatic or noncurable stage. PMID:24825748

  7. FGF Signaling in Prostate Cancer Progression

    Institute of Scientific and Technical Information of China (English)

    Nora M. NAVONE

    2009-01-01

    @@ Objective: prostate cancer is the second leading cause of cancer death in men in the United States. Localized prostate cancer can be cured by andro-gen ablation, but when the disease escapes the confines of the gland, the prospects for cure decrease drastically and the disease becomes "castrate resistant.

  8. Ractopamine in diets for finishing pigs of different sexual categories

    Directory of Open Access Journals (Sweden)

    Carlos Enrique da Trindade Barbosa

    2012-05-01

    Full Text Available Performance and carcass and cut yield of finishing pigs of three sexual categories fed diets with different levels of ractopamine were studied. Forty-eight hybrid animals (initial weight of 92.1±2.4 kg were distributed in a completely randomised design in 3 × 2 factorial arrangement (three sexual categories: surgically castrated males, two females and immunologically castrated males - with or without 10 ppm of ractopamine, totalling six treatments and eight repetitions with one animal per experimental plot during 28 days. Ractopamine improved weight gain and feed conversion of all sexual categories. The best results were obtained with immunologically castrated males, which, in turn, had lower carcass yield and backfat thickness in the belly. In the absence of ractopamine, depth and loin eye area were higher in females but no differences in these variables were observed between categories when this additive was used. Ractopamine increased the sirloin yield in all sexual categories. There was no difference in bonus index. Ractopamine improves the performance of pigs of 92 to 125 kg. Immunologically castrated males have the best performance responses to ractopamine, but with losses in carcass yield, loin characteristics and backfat thickness of the belly.

  9. Androgen-linked control of rat liver carbonic anhydrase III.

    OpenAIRE

    Shiels, A.; Jeffery, S; Phillips, I. R.; Shephard, E A; Wilson, C. A.; Carter, N D

    1983-01-01

    The concentration of carbonic anhydrase III (CAIII) in male rat liver was found to be 30 times greater than that in the female. Castration of male rats led to marked reduction in liver CAIII concentrations which could be partially restored to control levels by testosterone replacement. Marked developmental and senescence changes in liver CAIII were also observed in male rats.

  10. 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

  11. 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

  12. Heat production in growing pigs calculated according to the RQ and CN methods

    DEFF Research Database (Denmark)

    Christensen, K; Chwalibog, André; Henckel, S;

    1988-01-01

    1. Heat production, calculated according to the respiratory quotient methods, HE(RQ), and the carbon nitrogen balance method, HE(CN), was compared using the results from a total of 326 balance trials with 56 castrated male pigs fed different dietary composition and variable feed levels during the...

  13. Preservation of ovary function during combined treatment for cervical cancer

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2014-07-01

    Full Text Available Fixation of the preserved ovaries to uterine round ligament allow to retain ovarian function, not only during postoperative radiotherapy of stage Ib cervical cancer due to their transposition, but also after completing pelvic radiation because of preserved ovarian blood vessels in physiological place. This method prevents surgical and radiologic castration.

  14. Juvenile hormone stimulated synthesis of acyl-glycerols and Vitamin E in female accessory sexual glands of the fire bug, Pyrrhocoris apterus L

    Czech Academy of Sciences Publication Activity Database

    Jedlička, Pavel; Cvačka, Josef; Sláma, Karel

    2009-01-01

    Roč. 72, č. 1 (2009), s. 48-59. ISSN 0739-4462 Institutional research plan: CEZ:AV0Z50070508; CEZ:AV0Z40550506 Keywords : allatectomy * castration * juvenoid treatment Subject RIV: ED - Physiology Impact factor: 1.381, year: 2009

  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. 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".

  17. Pain management in the neonatal piglet during routine management procedures. Part 2: Grading the quality of evidence and the strength of recommendations

    Science.gov (United States)

    Piglets reared in swine production in the US undergo painful procedures that include castration, tail docking, teeth clipping, and identification with ear notching or tagging. These procedures are usually performed without pain mitigation. The objective of this project was to develop recommendations...

  18. ORGAN-PRESERVING OPERATIONS IN THE TREATMENT OF IMMATURE OVARIAN TERATOMA

    Directory of Open Access Journals (Sweden)

    I. Yu. Davydova

    2009-01-01

    Full Text Available Organ-preserving operations (OPO in patients with immature ovarian teratoma are shown to be a required technique that permits reproductive function to be preserved in young female patients. The most important positive aspect of OPO is also to preserve a normal hormonal background, owing to which surgical castration-related disorders may be prevented.

  19. 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

  20. Antiaging effect of Cordyceps sinensis extract.

    Science.gov (United States)

    Ji, Deng-Bo; Ye, Jia; Li, Chang-Ling; Wang, Yu-Hua; Zhao, Jiong; Cai, Shao-Qing

    2009-01-01

    This experiment studied the effect of Cordyceps sinensis extract (CSE) on mice aged by d-galactose and castrated rats to analyse its antiaging effect. Water maze and step-down type avoidance tests were used to examine the effect of CSE on learning and memory. CSE shortened escape latency, prolonged step-down latency and decreased the number of errors in mice aged by d-galactose. The effect of CSE on the sexual function of castrated rats was evaluated by measuring the penis erection latency, mount latency and ejaculation latency. CSE appeared to shorten penis erection latency and mount latency in castrated rats. The study also measured the effect of CSE on the activity of age-related enzymes. The results showed that CSE improved the activity of superoxide dismutase, glutathione peroxidase and catalase and lowered the level of lipid peroxidation and monoamine oxidase activity in the aged mice. The study demonstrated that CSE can improve the brain function and antioxidative enzyme activity in mice with d-galactose-induced senescence and promote sexual function in castrated rats. All of these findings suggest that CSE has an antiaging effect. PMID:18803231

  1. Efficacy of c-Met inhibitor for advanced prostate cancer

    International Nuclear Information System (INIS)

    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. 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. 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. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  2. Myasthenia gravis and masticatory muscle myositis in a dog

    OpenAIRE

    Clooten, Jennifer K.; Woods, J. P.; Smith-Maxie, Laura L.

    2003-01-01

    A 21-month-old, castrated male Vizsla was presented for pelvic limb weakness, difficulty opening his mouth, ptyalism, voice change, and urinary incontinence. Myasthenia gravis and masticatory myositis were diagnosed. The unusual clinical findings, diagnosis, treatment, and case outcome are described, followed by a brief discussion of myasthenia gravis and masticatory myositis.

  3. Effect of testosterone on morphine withdrawal syndrome in rats

    Institute of Scientific and Technical Information of China (English)

    Ali Reza Mohajjel Nayebi; Hassan Rezazadeh

    2008-01-01

    Aim: To determine whether testosterone is involved in morphine withdrawal syndrome (WS). Methods: In order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS. Results: The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, I.p.) male rats, WDS, AW, and J were signifi- cantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, I.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats. Confusion: It can be concluded that testosterone might be effectively involved in morphine WS.

  4. Listeria monocytogenes septicemia in an immunocompromised dog

    Science.gov (United States)

    An 11-year-old, male castrated, Boston terrier was presented to the North Carolina State University College of Veterinary Medicine Small Animal Emergency Service (NCSU-CVM-SAER) with a two-day history of progressive ataxia, left-sided head tilt, and anorexia. The dog had previously been diagnosed wi...

  5. Age-related changes in the percentage of oleate in adipose tissue of male and female Fischer rats

    DEFF Research Database (Denmark)

    Thorling, E.B.; Hansen, Harald S.

    1995-01-01

    weeks. Oestrogen injections twice a week to the castrated rats increased their oleate percentage within the same period to 23.4 ± 0.3%, partly reflecting the increase observed in the female rats. Stearic acid showed similar but less pronounced changes. The ratio oleic acid/stearic acid was constantly...

  6. The Nutritive value of mulberry leaves (Morus Alba) and partial replacement of cotton seed in rations on the performance of growing Vietnamese cattle

    NARCIS (Netherlands)

    Vu, C.C.; Verstegen, M.W.A.; Hendriks, W.H.; Pham, K.T.

    2011-01-01

    The in vivo digestibility of mulberry leaves (Morus alba) and the effects of the partial replacement of cotton seed with fresh mulberry leaf in rations on the performance of growing Vietnamese cattle was investigated. For the in vivo digestibility trial, twenty castrated rams of Phanrang breed (a lo

  7. Is Dexamethasone a Better Partner for Abiraterone Than Prednisolone?

    OpenAIRE

    Dizdar, Omer

    2015-01-01

    Dexamethasone may be a better partner for abiraterone compared with prednisolone in the treatment of metastatic castration-resistant prostate cancer. Upfront use of dexamethasone with abiraterone or a switch from prednisolone to dexamethasone at prostate-specific antigen progression might be feasible options and are currently being tested in larger trials.

  8. Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.

    OpenAIRE

    Drake, JM; Paull, EO; Graham, NA; Lee, JK; Smith, BA; Titz, B; Stoyanova, T; Faltermeier, CM; Uzunangelov, V; Carlin,, R.; Fleming, DT; Wong, CK; Newton, Y; Sudha, S; Vashisht, AA

    2016-01-01

    We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of drugga...

  9. Regulation of surfactant protein D in the rodent prostate

    Directory of Open Access Journals (Sweden)

    Maldonado Cristina A

    2007-11-01

    Full Text Available Abstract Background Surfactant protein D (SP-D is an innate immune protein that is present in mucosal lined surfaces throughout the human body, including the male reproductive tract. In the present study, we characterized the regulation of SP-D expression in the mouse and rat prostate. Methods Real time reverse transcriptase polymerase chain reaction (RT-PCR and immunostaining were used to characterize SP-D mRNA and protein in the mouse male reproductive tract. In order to evaluate the effects of testosterone on SP-D gene expression, we measured SP-D mRNA levels via real time RT-PCR in prostates from sham-castrated mice and castrated mice. In addition, we used a rat prostatitis model in which Escherichia coli was injected into the prostate in vivo to determine if infection influences SP-D protein levels in the prostate. Results We found that SP-D mRNA and protein are present throughout the mouse male reproductive tract, including in the prostate. We determined that castration increases prostate SP-D mRNA levels (~7 fold when compared to levels in sham-castrated animals. Finally, we demonstrated that infection in the prostate results in a significant increase in SP-D content 24 and 48 hours post-infection. Conclusion Our results suggest that infection and androgens regulate SP-D in the prostate.

  10. 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

  11. Androgens and androgen receptors in prostatic cancer

    NARCIS (Netherlands)

    O.G.J.M. van Aubel (Olav)

    1989-01-01

    textabstractOur understanding of the testicular control of growth and functioning of the accessory sex glands began with an observation in the 18th century of John Hunter (1), who discovered in animals the endocrine dependency of the prostate. He demonstrated that castration in experimental animals

  12. Selective cell death mediated by small conditional RNAs:a novel therapeutic approach to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Che-Kai Tsao; William K Oh

    2011-01-01

    @@ Targeted molecular therapy has been an elusive goal in the treatment of neo-plastic diseases.While chemotherapy has improved the outcome of many cancers, a non-selective cytotoxic approach invariably causes damage to normal cells, resulting in side effects and limiting treatment efficacy.This is evident in the evolution of treatment for castration-resistant prostate cancer (CRPC).

  13. 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.

  14. Dietary tryptophan and threonine supply to 28 days old weaned piglets

    DEFF Research Database (Denmark)

    Fernández, José Adalberto; Strathe, Anders Bjerring

    2009-01-01

    The effects of dietary levels of tryptophan (TRP) and threonine (THR) on appetite, growth performance and faecal score were assessed in an experiment with 360 weaned piglets. Littermate male castrates and females (1:1), weaned at 28 days of age, were given free access to feed during 28 days. Six...

  15. 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

  16. Metabolic syndrome and androgen deprivation therapy in metabolic complications of prostate cancer patients

    Institute of Scientific and Technical Information of China (English)

    YUAN Jia-qi; XU Tao; ZHANG Xiao-wei; YU Lu-ping; LI Qing; LIU Shi-jun; HUANG Xiao-bo; WANG Xiao-feng

    2012-01-01

    Background Incidence of prostate cancer in Chinese males grows significantly in the past decades.Androgen deprivation therapy has been generally employed in the treatment of locally advanced and metastatic prostate cancer for many years,yet only little data was known about the metabolic syndrome in patients receiving hormonal therapy.This study described the prevalence and the changing trends of hormone-related metabolic complications,and analyzed their correlation with different therapies.Methods In 125 patients treated with castration or maximal androgen blockage for at least 12 months,metabolic indicators were analyzed.Results Totally,13.5% patients in castration group and 30.1% patients in maximal androgen blockage group were diagnosed metabolic syndrome 12 months after the beginning of treatments (x2=4.739,P=0.029).In castration group,increased triglyceride and decreased high-density lipoprotein-cholesterol were significant at the month 12,increased fasting plasma glucose and blood pressure were significant at the month 4.In maximal androgen blockage group,increased triglyceride and decreased high-density lipoprotein-cholesterol were significant at the month 4,increased fasting plasma glucose and blood pressure were significant at the month 8.Total testosterone and free testosterone in maximal androgen blockage group were significantly lower than castration group at all visits,which were proved to show positive or negative correlations with metabolic indications.Severity of metabolic complications in maximal androgen blockage group was generally more serious than people received castration,with significantly statistical difference or not.Trends of high-density lipoprotein-cholesterol and fasting plasma glucose were significant different between two kinds of therapy (P=0.005,P=0.019,respectively).Conclusions Prostate cancer patients receiving androgen deprivation therapy were at high risk of suffering metabolic syndrome.Severity of metabolic complications

  17. Androgenic control of male-typical behavior, morphology and sex recognition is independent of the mode of sex determination: A case study on Lichtenfelder's gecko (Eublepharidae: Goniurosaurus lichtenfelderi).

    Science.gov (United States)

    Golinski, Alison; Kubička, Lukáš; John-Alder, Henry; Kratochvíl, Lukáš

    2015-06-01

    Previous work on lizards has shown that many sexually dimorphic traits depend on testosterone (T), but the details of this control can vary among species. Here, we tested the role of T on the expression of morphological, physiological, and behavioral traits in Lichtenfelder's gecko (Goniurosaurus lichtenfelderi), from the lizard family Eublepharidae notable for interspecific variation in sexually dimorphic traits and the mode of sex determination. Experiments included three groups of males (intact control, surgically castrated, castrated with T replacement) and two groups of females (intact control, T supplemented). In males, castration caused reductions in 1) the size of hemipenes, 2) offensive aggression, 3) male sexual behavior in a neutral arena, 4) activity of precloacal glands, and 5) loss of male chemical cues for sex recognition. These reductions were not observed in castrated males with T replacement. Interestingly, castrated males performed sexual behavior in their home cages, which shows that the effect of T depends on the environmental context. Notably, tail vibration, previously reported as a courtship behavior in other eublepharids, is displayed by males of G. lichtenfelderi during interactions with conspecifics of both sexes, suggesting an evolutionary shift in the meaning of this signal. In females, T induced growth of hemipenes and male-typical courtship but did not induce precloacal pore activity, aggression, or mounting. In comparison to previous reports on Eublepharis macularius, our results indicate that effects of T do not depend on the mode of sex determination. Further, our results extend our understanding of the complexity of control of male traits and illustrate how lability in the effects of T can be a general mechanism causing evolutionary changes in the components of suites of functionally correlated traits. PMID:25967849

  18. Prolonged androgen deprivation may influence the autoregulation of estrogen receptors in the brain and pelvic floor muscles of male rats.

    Science.gov (United States)

    Wibowo, Erik; Calich, Hannah J; Currie, R William; Wassersug, Richard J

    2015-06-01

    Androgen deprivation in males has detrimental effects on various tissues and bodily functions, some of which can be restored by estradiol (E2) administration. We investigated how the duration of androgen deprivation affects the autoregulation of estrogen receptors (ERs) levels in core brain areas associated with sexual behavior and cognition, as well as in pelvic floor muscles (PFM). We also measured c-Fos levels in brain areas associated with sexual behavior shortly after the rats mated. Prolonged castration increases ERα levels in the preoptic area (POA) and E2 treatment reverses these effects. In the POA, c-Fos levels after mating are not affected by the duration of androgen deprivation and/or E2 treatment. ERβ levels in the POA as well as c-Fos levels in the POA and the core area of nucleus accumbens correlate with the mounting frequency for E2-treated Short-Term castrates. Additionally, ERβ levels in the medial amygdala are positively correlated with the mounting frequency of Long-Term castrates that received E2 treatment. In the hippocampus, ERs are downregulated only when E2 is administered early after castration, whereas downregulation of ERα in the prefrontal cortex only occurs with delayed E2 treatment. Early, but not delayed, E2 treatment after castration increases ERβ levels in the bulbocavernosus and ERα levels in the levator ani of male rats. Our data suggest that the duration of androgen deprivation may influence the autoregulation of ERs by E2 treatment in select brain areas and pelvic floor muscles of male rats. PMID:25746452

  19. The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects

  20. Anti-Müllerian hormone (AMH) profiles as a novel biomarker to evaluate the existence of a functional cryptorchid testis in Japanese Black calves.

    Science.gov (United States)

    Kitahara, Go; El-Sheikh Ali, Hossam; Sato, Tomohiro; Kobayashi, Ikuo; Hemmi, Koichiro; Shirao, Yuka; Kamimura, Shunichi

    2012-01-01

    Anti-Müllerian hormone (AMH) and testosterone (T) profiles in blood were investigated before and after an hCG stimulation test to assess their sensitivity and specificity for the existence of a functional cryptorchid testis in Japanese Black calves. The hCG (3,000 IU) was administered on Day 0, and peripheral blood was collected on Days 0 (just before hCG injection), 5 and 7 in intact male calves (Intact; n=19), bilateral castrated calves (Castrated; n=17), unilateral cryptorchid calves, which abdominal testis could been extracted (Uni-crypto; n=9). Castration of a descended testis was carried in the Castrated and Uni-Crypto groups on Day -14. The AMH detectability and the optimum cut-off point for T levels using the receiver operating characteristic curve were verified to characterize the cryptorchid testis. AMH values on Day 0 were 21.1 ± 5.1 and 29.0 ± 7.5 ng/ml in the Intact and Uni-crypto groups, respectively (Mean ± SEM). AMH levels were under the detection limit in the Castrated group (i.e., crypto group. The detectable levels for AMH was 0.006 ng/ml, and the optimum cut-off point for T was 0.9 ng/ml; the sensitivity and specificity for evaluation of testicular descent into the scrotum were 1.0 for both the AMH and T levels. The detection rates in the Uni-crypto group using them were 1.0 and 0.57 for AMH on Day 0 and T on Days 5 or 7, respectively. In conclusion, plasma AMH profiles could be used as a novel biomarker to evaluate the existence of a functional cryptorchid testis in Japanese Black calves. PMID:22322144