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Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
March 20, 2018: Prostate Cancer and Prostatic Diseases
Luke C Peng, Amol K Narang, Carol Gergis, Noura A Radwan, Peijin Han, Ariel E Marciscano, Scott P Robertson, Pei He, Janson Trieu, Ashwin N Ram, Todd R McNutt, Emily Griffith, Theodore A DeWeese, Stephanie Honig, Harleen Singh, Stephen C Greco, Phuoc T Tran, Curtiland Deville, Theodore L DeWeese, Daniel Y Song
OBJECTIVES: Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). MATERIAL AND METHODS: We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution...
March 15, 2018: Urologic Oncology
Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Gustavo Rubio, Alison J Birtle, Nicolas Delanoy, Joaquim Bellmunt, Stéphane Oudard
BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC)...
February 23, 2018: Clinical Genitourinary Cancer
Nicholas Russell, Rudolf Hoermann, Ada S Cheung, Michael Ching, Jd Zajac, David J Handelsman, Mathis Grossmann
OBJECTIVE: There is increasing recognition that, in men, some biological actions attributed to testosterone (T) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short term biological effects of E2 addback without increasing circulating T. DESIGN: 28-day randomised, placebo-controlled trial Methods: 37 participants were randomised to either 0...
March 16, 2018: European Journal of Endocrinology
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
L Klotz, A Loblaw, R Siemens, P Ouellette, A Kapoor, M Kebabdjian, L Zhang, F Saad
BACKGROUND: In men initiating intermittent androgen deprivation therapy (IADT), a range of induction durations, between 3 and 12 months, have been employed. OBJECTIVE: To determine if the duration of induction ADT influences the duration of the off treatment interval and the recovery of serum testosterone (T). MANEUVER: This was a prospective, randomized, open label study. Men with biochemical recurrence after local therapy for prostate cancer, with a negative bone scan, were randomized between 4 and 10 months of monthly Degarelix...
March 10, 2018: Journal of Urology
Derek S Tsang, Jennifer M Jones, Osai Samadi, Suhayb Shah, Nicholas Mitsakakis, Charles N Catton, William Jeon, Joshua To, Henriette Breunis, Shabbir M H Alibhai
PURPOSE: To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials...
March 12, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Laurence Guillaumie, Alice Ndayizigiye, Clément Beaucage, Jocelyne Moisan, Jean-Pierre Grégoire, Denis Villeneuve, Sophie Lauzier
Objectives: Patients prescribed antidepressant drug treatment (ADT) for major depression report several needs in relation to their treatment, and a large proportion of these patients will end ADT prematurely. Community pharmacists may play an important role in monitoring ADT and supporting these patients. However, little is known about patient experiences of the services provided in community pharmacies. The objectives of this study were to 1) explore patients' experiences with the services community pharmacists provide for ADT and 2) identify potential avenues for improvement of pharmacists' services within the context of ADT...
March 2018: Canadian Pharmacists Journal: CPJ, Revue des Pharmaciens du Canada: RPC
Matthew R Sydes, Melissa R Spears, Malcolm D Mason, Noel W Clarke, David P Dearnaley, Johann S de Bono, Gert Attard, Simon Chowdhury, Bill Cross, Silke Gillessen, Zaf Malik, Rob Jones, Chris Parker, Alastair W S Ritchie, J Martin Russell, Robin Millman, David Matheson, Claire Amos, Clare Gilson, Alison Birtle, Susannah Brock, Lisa Capaldi, Prabir Chakraborti, Ananya Choudhury, Linda Evans, Daniel Ford, Joanna Gale, Stephanie Gibbs, Duncan Gilbert, Robert Hughes, Duncan McLaren, Jason Lester, Ashok Nikapota, Joe O'Sullivan, Omi Parikh, Clive Peedell, Andrew Protheroe, Sarah M Rudman, Richard Shaffer, Denise Sheehan, Matthew Simms, Narayanan Srihari, Räto Strebel, Santhanam Sundar, Shaun Tolan, David Tsang, Mohini Varughese, John Wagstaff, Mahesh K B Parmar, Nicholas D James
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013...
February 26, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Ivan Grbatinić, Nebojsa Milosevic, Dusica Maric
The aim of this study is to determine whether the dentate neurons can be translaminary neuromorphotopologically classified as ventrolateral or dorsomedial type. Adult human dentate 2D binary interneuron images are used for the purposes of the analysis. The analysis is performed on the real and the virtual neuron sample. The total of 29 parameters is used. They can be divided into the classes: neuron surface, shape, length, branching and complexity. The clustering is performed through the algorithm consisted from of the steps of predictor extraction (matrix attractor analysis/non-negative matrix factorization and cluster analysis of predictor factors, separate unifactor analysis/Student's t-test and MANOVA) and multivariate cluster analysis set (cluster analysis, principal component analysis, factor analysis with pro/varimax rotation, Fisher's linear discriminant analysis and feed-forward backpropagation artificial neural networks)...
2018: Journal of Integrative Neuroscience
Ricarda Höhner, Joaquim V Marques, Tetsuro Ito, Yoshiaki Amakura, Alan D Budgeon, Karl Weitz, Kim K Hixson, Laurence B Davin, Helmut Kirchhoff, Norman G Lewis
Arogenate dehydratase (ADT) catalyzes the final step of phenylalanine (Phe) biosynthesis. Previous work showed that ADT-deficient Arabidopsis thaliana mutants had significantly reduced lignin contents, with stronger reductions in lines that had deficiencies in more ADT isoforms. Here, by analyzing Arabidopsis ADT mutants using our phenomics facility and UPLC-MS based metabolomics, we describe the effects of modulation of ADT on photosynthetic parameters and secondary metabolism. Our data indicate that a reduced carbon flux into Phe biosynthesis in ADT mutants impairs the consumption of photosynthetically produced ATP leading to an increased ATP/ADP ratio, the over-accumulation of transitory starch, and lower electron transport rates...
March 9, 2018: Plant Physiology
Myong Kim, Cheryn Song, In Gab Jeong, Seung-Kwon Choi, Myungchan Park, Myungsun Shim, Young Seok Kim, Dalsan You, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn
BACKGROUND: Here we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer. METHODS: Patients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression...
March 9, 2018: BMC Cancer
Alicia K Morgans, Yu-Hui Chen, Christopher J Sweeney, David F Jarrard, Elizabeth R Plimack, Benjamin A Gartrell, Michael A Carducci, Maha Hussain, Jorge A Garcia, David Cella, Robert S DiPaola, Linda J Patrick-Miller
Purpose Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone. Methods Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months...
March 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Alessandro Magli, Eugenia Moretti, Annarita Tullio, Gianluca Giannarini, Fabrizio Tonetto, Mauro Urpis, Margherita Crespi, Claudio Foti, Agnese Prisco, Margherita Polsinelli, Gioacchino De Giorgi, Giulia Bravo, Paolo Scalchi, Marco Trovò
OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012...
March 8, 2018: Prostate Cancer and Prostatic Diseases
Chen Zhao, Qing Bi, Mingguang Bi
BACKGROUND: Treatment of a type II tibial eminence avulsion fracture was controversial. The aim of this study was to compare the clinical outcomes of a modified arthroscopic suture fixation versus conservative immobilization in treatment of this type fracture in immature population. METHODS: A total of 43 type II avulsion fractures of tibial intercondylar eminence in immature patients were retrospectively enrolled in the study. Twenty-two (13 males, 9 females) were treated with arthroscopic suture fixation and 21(12 males, 9 females) with conservative cast immobilization...
March 7, 2018: International Orthopaedics
Sophie Lauzier, Hichem Kadachi, Jocelyne Moisan, Alain Vanasse, Alain Lesage, Marie-Josée Fleury, Jean-Pierre Grégoire
OBJECTIVE: To assess whether neighbourhood deprivation is associated with exposure to an antidepressant drug treatment (ADT) and its quality among individuals diagnosed with unipolar depression and insured by the Quebec public drug plan. METHOD: We conducted an administrative database cohort study of adults covered by the Quebec public drug plan who were diagnosed with a new episode of unipolar depression. We assessed material and social deprivation using an area-based index...
January 1, 2018: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Sam Egger, Suzanne Hughes, David P Smith, Suzanne Chambers, Clare Kahn, Annette Moxey, Dianne L O'Connell
OBJECTIVE: To assess whether the use of complementary and alternative medicines therapies (CAMs) for prostate cancer and/or its treatment side effects by long-term survivors is associated with selected socio-demographic, clinical, health-related quality-of-life (HRQOL) and/or psychological factors. DESIGN, SETTING AND PARTICIPANTS: The Prostate Cancer Care and Outcomes Study (PCOS) is a population-based cohort study of men with prostate cancer who were aged less than 70 years at diagnosis in New South Wales, Australia...
2018: PloS One
Christopher J D Wallis, Raj Satkunasivam, Sender Herschorn, Calvin Law, Arun Seth, Ronald T Kodama, Girish S Kulkarni, Robert K Nam
BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. We sought to examine the effect of ADT on nonprostate cancer mortality among patients with nonmetastatic prostate cancer. METHODS: We performed a population-based, retrospective cohort study of men aged 66 years and older treated with surgery or radiotherapy for nonmetastatic prostate cancer in Ontario, Canada from 2002 to 2009 using administrative datasets (including the Ontario Cancer Registry, Ontario Drug Benefit, and Ontario Health Insurance Plan)...
March 1, 2018: Urologic Oncology
Zineb Hamilou, Giulia Baciarello, Karim Fizazi
Both docetaxel+androgen deprivation therapy (ADT) and abiraterone acetate 1000mg/d+prednisone/prednisolone 5mg/d+ADT improved survival in patients with metastatic castration-naive prostate cancer. Their use should be offered and guided by patient's own characteristics.
February 27, 2018: European Urology Focus
Nina-Sophie Schmidt-Hegemann, Wolfgang Peter Fendler, Harun Ilhan, Annika Herlemann, Alexander Buchner, Christian Stief, Chukwuka Eze, Paul Rogowski, Minglun Li, Peter Bartenstein, Ute Ganswindt, Claus Belka
BACKGROUND: PSMA PET/CT visualises prostate cancer residual disease or recurrence at lower PSA levels compared to conventional imaging and results in a change of treatment in a remarkable high number of patients. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival. Thus, it can be hypothesised that PSMA PET/CT-based radiotherapy might improve the prognosis of these patients. METHODS: One hundred twenty-nine patients underwent PSMA PET/CT due to biochemical persistence (52%) or recurrence (48%) after radical prostatectomy without evidence of distant metastases (February 2014-May 2017) and received PSMA PET/CT-based radiotherapy...
March 2, 2018: Radiation Oncology
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