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castration refractory

Jean-Pierre Droz, Gilles Albrand, Silke Gillessen, Simon Hughes, Nicolas Mottet, Stéphane Oudard, Heather Payne, Martine Puts, Gilbert Zulian, Lodovico Balducci, Matti Aapro
CONTEXT: Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE: To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease...
January 11, 2017: European Urology
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Filip Poelaert, Candy Kumps, Nicolaas Lumen, Stephanie Verschuere, Louis Libbrecht, Marleen Praet, Sylvie Rottey, Tom Claeys, Piet Ost, Karel Decaestecker, Gert De Meerleer, Charles Van Praet
OBJECTIVES: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. MATERIALS AND METHODS: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients...
January 5, 2017: Urologia Internationalis
Giuseppe Cicero, Rossella De Luca, Patrizia Dorangricchia, Antonio Galvano, Giuseppe Lo Re, Vincenzo Serretta, Nino Dispensa, Francesco Dieli
PURPOSE: The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. METHODS: Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m2 every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously...
December 14, 2016: Oncology
Wolfgang Roll, Axel Bode, Matthias Weckesser, Martin Bögemann, Kambiz Rahbar
Recently radiolabeled ligands targeting prostate specific membrane antigen (PSMA) have been introduced for diagnostics and treatment of prostate cancer. Labeled with Lutetium, PSMA radioligand therapy (RLT) is one of the most promising new treatments of metastatic castration refractory prostate cancer. We present images of Ga-PSMA PET/CT and parameters of response of a 75-year-old heavily pretreated metastatic castration refractory prostate cancer patient with extended bone metastases, showing an extraordinary biochemical response in PSA-levels concordant to SUV decline in bone metastases...
December 3, 2016: Clinical Nuclear Medicine
Erik Wibowo, Richard J Wassersug
INTRODUCTION: There is much popular discussion on strategies to facilitate multiple orgasms in men (ie, 100,000+ hits in Google), yet the topic has not received an objective comprehensive review in the literature. AIM: To review the literature on male multiple orgasms. METHODS: We searched the literature for publications on "male multiple orgasms" and factors influencing male multiple orgasms in Google, PubMed, and PsychINFO. This yielded 15 relevant publications...
April 2016: Sexual Medicine Reviews
Nada Lallous, Eric Leblanc, Ravi S N Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new antiandrogens, such as enzalutamide, or androgen synthesis inhibitors like abiraterone has improved patient outcomes in the treatment of advanced prostate cancer. However, due to the development of drug resistance and tumor cell survival, a majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
December 2016: Molecular Cancer Therapeutics
Yohei Sekino, Naohide Oue, Yoshinori Shigematsu, Akira Ishikawa, Naoya Sakamoto, Kazuhiro Sentani, Jun Teishima, Akio Matsubara, Wataru Yasui
OBJECTIVES: Prostate cancer (PCa) is a common malignancy worldwide. Docetaxel has been an important treatment option for patients with metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients with CRPC treated with docetaxel eventually become refractory. In the present study, we analyzed the expression and distribution of kinesin family member C1 (KIFC1) in human PCa by immunohistochemistry and examined the effect of inhibiting KIFC1 expression on docetaxel resistance...
January 2017: Urologic Oncology
Xiao Wei, Carl Schlenkhoff, Claudia Sopora, Markus Essler, Hojjat Ahmadzadehfar
An 81-year-old castrate-resistant prostate cancer man with multiple lymph node, bone, and hepatic metastases received four cycles of Lu-PSMA-617 treatments at our department from May to December 2015. All of his liver metastases showed PSMA expression in Ga-PSMA PET performed before the first cycle. Under this therapy, all of the metastases showed significant regression in size and PSMA expression over time.
November 2016: Clinical Nuclear Medicine
Justin Ferdinandus, Elisabeth Eppard, Florian Gärtner, Stefan Kürpig, Rolf Fimmers, Anna Yordanova, Stefan Hauser, Georg Feldmann, Markus Essler, Hojjat Ahmadzadehfar
PURPOSE: Radioligand therapy (RLT) with (177)Lu-PSMA-617 (Lu-PSMA-617) (prostate-specific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pre-therapeutic parameters on the therapeutic response measured by prostate-specific antigen(PSA) two months after RLT. METHODS: RLT was performed in 40 hormone and/or chemo refractory patients with distant metastases and progressive disease (mean age: 71...
September 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Diogo A Bastos, Emmanuel S Antonarakis
Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR)-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide...
2016: Drug Design, Development and Therapy
Daisuke Nakata, Kazuhide Nakayama, Tsuneo Masaki, Akira Tanaka, Masami Kusaka, Tatsuya Watanabe
BACKGROUND: Castration resistance creates a significant problem in the treatment of prostate cancer. Constitutively active splice variants of androgen receptor (AR) have emerged as drivers for resistance to androgen deprivation therapy, including the next-generation androgen-AR axis inhibitors abiraterone and enzalutamide. In this study, we describe the characteristics of a novel castration-resistant prostate cancer (CRPC) model, designated JDCaP-hr (hormone refractory). METHODS: JDCaP-hr was established from an androgen-dependent JDCaP xenograft model after surgical castration...
December 2016: Prostate
Meihua Liang, Fei Zhan, Juan Zhao, Qi Li, Jiazi Wuyang, Guannan Mu, Dianjun Li, Yanqiao Zhang, Xiaoyi Huang
BACKGROUND: Platinum-based chemotherapy is emerging as the first line of treatment for castration resistant prostate cancer. Among the family of platinum (IV)-based compounds, a member known as CPA-7 inhibits the growth of multiple cancer cell lines. However, how and to what extent CPA-7 elicits its anti-prostate cancer effects in vivo is largely unknown. METHODS: In this study, we firstly assessed the potential toxicity of the synthesized CPA-7 in a prostate cancer model as well as in normal mice...
2016: BMC Cancer
Nicholas James, Sarah Pirrie, Ann Pope, Darren Barton, Lazaros Andronis, Ilias Goranitis, Stuart Collins, Duncan McLaren, Joe O'Sullivan, Chris Parker, Emilio Porfiri, John Staffurth, Andrew Stanley, James Wylie, Sharon Beesley, Alison Birtle, Janet Brown, Prabir Chakraborti, Martin Russell, Lucinda Billingham
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...
July 2016: Health Technology Assessment: HTA
Georgios Kallifatidis, James J Hoy, Bal L Lokeshwar
Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease...
October 2016: Seminars in Cancer Biology
Eva De Mol, R Bryn Fenwick, Christopher T W Phang, Victor Buzón, Elzbieta Szulc, Alex de la Fuente, Albert Escobedo, Jesús García, Carlos W Bertoncini, Eva Estébanez-Perpiñá, Iain J McEwan, Antoni Riera, Xavier Salvatella
Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer...
September 16, 2016: ACS Chemical Biology
Sarah M Schwarzenböck, Matthias Eiber, Günther Kundt, Margitta Retz, Monique Sakretz, Jens Kurth, Uwe Treiber, Roman Nawroth, Ernst J Rummeny, Jürgen E Gschwend, Markus Schwaiger, Mark Thalgott, Bernd J Krause
PURPOSE: The aim of this study was to prospectively evaluate the value of [(11)C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. METHODS: Thirty-two patients were referred for [(11)C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
Andrea K Miyahira, Jonathan W Simons, Howard R Soule
The 22nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat was convened in Washington, D.C. from October 8 to 10, 2015. This event is the foremost scientific conference in the world focusing on basic, translational, and clinical prostate cancer research with the highest potential for accelerating the understanding of prostate cancer biology and improving the lives and outcomes of prostate cancer patients. Topics highlighted during the 2015 Retreat included: (i) new strategies and treatments for localized high-risk, hormone-naïve, oligometastatic, castrate-resistant, and treatment-refractory prostate cancer settings; (ii) the biology and genomics of tumor heterogeneity and tumor evolution; (iii) new understandings on the mechanisms and targeting of oncogenic drivers of prostate cancer; (iv) bioengineering of novel therapies and drug delivery methods; (v) innovative approaches to tumor immunotherapy; (vi) emerging molecular imaging technologies with improved sensitivity and specificity; and (vii) advancements in prognostic and predictive biomarkers and precision medicine strategies...
September 2016: Prostate
L Andronis, I Goranitis, S Pirrie, A Pope, D Barton, S Collins, A Daunton, D McLaren, J O'Sullivan, C Parker, E Porfiri, J Staffurth, A Stanley, J Wylie, S Beesley, A Birtle, J Brown, P Chakraborti, S Hussain, M Russell, L Billingham, N James
OBJECTIVES: To evaluate the cost-effectiveness of adding zoledronic acid (ZA) or strontium-89 (Sr89) to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC). PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2x2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs...
June 3, 2016: BJU International
M Luz Flores, Carolina Castilla, Jessica Gasca, Rafael Medina, Begoña Pérez-Valderrama, Francisco Romero, Miguel A Japón, Carmen Sáez
Prostate cancer is the leading cause of cancer-related death among men in developed countries. Although castration therapy is initially effective, prostate cancers progress to hormone-refractory disease and in this case taxane-based chemotherapy is widely used. Castration-resistant prostate cancer cells often develop resistance to chemotherapy agents and the search for new therapeutic strategies is necessary. In this article, we demonstrate that PKCδ silencing favors mitotic arrest after paclitaxel treatment in PC3 and LNCaP cells; however, this is associated with resistance to paclitaxel-induced apoptosis...
July 2016: Molecular Cancer Therapeutics
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