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https://www.readbyqxmd.com/read/27924136/prognostic-value-of-inflammation-in-prostate-cancer-progression-and-response-to-therapeutic-a-critical-review
#1
REVIEW
Alessandro Sciarra, Alessandro Gentilucci, Stefano Salciccia, Federico Pierella, Flavio Del Bianco, Vincenzo Gentile, Ida Silvestri, Susanna Cattarino
Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a factor involved in prostate cancer (PC) pathogenesis and progression. This review critically analyzes the role of inflammation as a prognostic factor for progression and aggressiveness of PC. We verified the last 10 years literature data on the association between inflammation and PC aggressiveness, or PC response to therapies...
2016: Journal of Inflammation
https://www.readbyqxmd.com/read/27922871/excellent-response-to-177lu-psma-617-radioligand-therapy-in-a-patient-with-advanced-metastatic-castration-resistant-prostate-cancer-evaluated-by-68ga-psma-pet-ct
#2
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
https://www.readbyqxmd.com/read/27919973/bone-targeted-novel-cytotoxic-polybisphosphonate-conjugate-in-castration-resistant-prostate-cancer-a-multicenter-phase-1-study
#3
Camilla Thellenberg-Karlsson, Claes Nyman, Sten Nilsson, René Blom, Marcela Márquez, Enrique Castellanos, Anders R Holmberg
BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919966/multimodal-primary-treatment-of-metastatic-prostate-cancer-with-androgen-deprivation-and-radiation
#4
Timo Joensuu, Greetta Joensuu, Kalevi Kairemo, Timo Kiljunen, Maigo Riener, Aili Aaltonen, Martti Ala-Opas, Aki Kangasmäki, Tuomo Alanko, Lauri Taipale, Petteri Hervonen, Anna Bützow, Irene Virgolini, Akseli Hemminki
AIM: We combined anti-androgen therapy with radiotherapy in a first-line setting for metastatic prostate cancer aiming to cause maximal cancer-cell death to delay the emergence of castration-resistant disease. MATERIALS AND METHODS: In this non-randomized retrospective series of 46 patients, the initial median prostate-specific antigen (PSA) was 98.5 μg/l (range=6.7-15,500), median Gleason score 9 and most men had at least T3N1M1 disease. All patients received luteinizing hormone releasing hormone analog or degarelix with bicalutamide...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27916908/epidermal-growth-factor-receptor-status-in-circulating-tumor-cells-as-a-predictive-biomarker-of-sensitivity-in-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-chemotherapy
#5
Takatsugu Okegawa, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) can be used to predict survival in a population of bone-metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel chemotherapy. METHODS: All patients with mCRPC who had experienced treatment failure with androgen-deprivation therapy and had received docetaxel chemotherapy were eligible. CTCs and EGFR expression in CTCs were enumerated with the CellSearch System in whole blood...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916435/analytical-validation-of-androgen-receptor-splice-variant-7-detection-in-a-clinical-laboratory-improvement-amendments-clia-laboratory-setting
#6
Parvez M Lokhandwala, Stacy L Riel, Lisa Haley, Changxue Lu, Yan Chen, John Silberstein, Yezi Zhu, Gang Zheng, Ming-Tseh Lin, Christopher D Gocke, Alan W Partin, Emmanuel S Antonarakis, Jun Luo, James R Eshleman
Patients with castration-resistant prostate cancer (CRPC) often are treated with drugs that target the androgen receptor (AR) ligand-binding domain. Constitutively active AR splice variant 7 (AR-V7) lacks the ligand-binding domain and, if detected in circulating tumor cells, may be associated with resistance to these agents. We validated an AR-V7 assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Circulating tumor cells were isolated, and mRNA was reverse-transcribed into cDNA...
December 1, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27916295/association-of-biomarkers-with-serious-cardiac-adverse-events-during-abiraterone-acetate-treatment-in-castration-resistant-prostate-cancer
#7
REVIEW
Sara Campora, Eleonora Campazzi, Silvia Zanardi, Matteo Puntoni, Marco Piccininno, Arnoldo Piccardo, Mehrdad Shoushtari Zadeh Naseri, Carlotta Defferrari, Nicoletta Provinciali, Marilena Petrera, Domenico Marra, Ennio Biscaldi, Gian Carlo Antonucci, Damiano Ricci, Matteo Clavarezza, Alessandra Gennari, Alberto Gozza, Mauro D'Amico, Marco Mori, Andrea DeCensi
BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#8
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27911459/evaluation-of-bone-metastases-by-18f-choline-pet-ct-in-a-patient-with-castration-resistant-prostate-cancer-treated-with-radium-223
#9
Piera Scalzi, Cinzia Baiocco, Sabrina Genovese, Antonella Trevisan, Zuzana Sirotova, Carlo Poti
BACKGROUND: To date, bone metastases remain the main cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer (mCRPC). Therefore, the combination of accurate early detection of bony disease and effective treatment of these lesions is crucial in the management of mCRPC patients, but clinical trials specifically designed to test novel approaches are currently lacking. CASE DESCRIPTION: This report describes the case of a 74-year-old male with bone mCRPC and symptomatic and biochemical progression, who underwent radium-223 therapy, following previous treatment failure...
December 2, 2016: Urologia
https://www.readbyqxmd.com/read/27910803/the-prognostic-and-predictive-value-of-tmprss2-erg-gene-fusion-and-erg-protein-expression-in-prostate-cancer-biopsies
#10
Kasper Drimer Berg
BACKGROUND: The clinical course of prostate carcinoma (PCa) is very heterogeneous. Consequently, a personalised approach for risk stratification and treatment planning is important. Recently, it has become evident that PCa, also at the genomic level, is heterogeneous. An early and common alteration is the gene fusion between the transmembrane protease serine 2 (TMPRSS2) gene and the v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene resulting in expression of the oncoprotein ERG...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#11
Jean-Pascal Henry Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
November 30, 2016: Oncologist
https://www.readbyqxmd.com/read/27903893/identification-of-a-novel-k311-ubiquitination-site-critical-for-androgen-receptor-transcriptional-activity
#12
Urszula L McClurg, David M W Cork, Steven Darby, Claudia A Ryan-Munden, Sirintra Nakjang, Leticia Mendes Côrtes, Achim Treumann, Luke Gaughan, Craig N Robson
The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance. Here, we report a novel N-terminal ubiquitination site at lysine 311. Ubiquitination of this site plays a role in AR stability and is critical for its transcriptional activity...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27900064/enzalutamide-induced-acute-generalized-exanthematous-pustulosis
#13
Chloé Alberto, Maria Polina Konstantinou, Catherine Martinage, Eline Casassa, Emilie Tournier, Haleh Bagheri, Vincent Sibaud, Loïc Mourey, Juliette Mazereeuw-Hautier, Nicolas Meyer, Carle Paul, Cristina Bulai Livideanu
INTRODUCTION: Enzalutamide (Xtandi®) is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. OBJECTIVE: We report the first case of acute generalized exanthematous pustulosis (AGEP) induced by enzalutamide. OBSERVATION: A 62-year-old male patient with no significant medical history, was diagnosed in April 2014 with metastatic prostatic adenocarcinoma...
November 13, 2016: Journal of Dermatological Case Reports
https://www.readbyqxmd.com/read/27899381/castration-resistance-in-prostate-cancer-is-mediated-by-the-kinase-nek6
#14
Atish D Choudhury, Anna C Schinzel, Maura B Cotter, Rosina T Lis, Katherine Labella, Ying Jie Lock, Francesca Izzo, Isil Guney, Michaela Bowden, Yvonne Y Li, Jinal Patel, Emily Hartman, Steven A Carr, Monica Schenone, Jacob D Jaffe, Philip W Kantoff, Peter S Hammerman, William C Hahn
In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27897170/truncation-and-constitutive-activation-of-the-androgen-receptor-by-diverse-genomic-rearrangements-in-prostate-cancer
#15
Christine Henzler, Yingming Li, Rendong Yang, Terri McBride, Yeung Ho, Cynthia Sprenger, Gang Liu, Ilsa Coleman, Bryce Lakely, Rui Li, Shihong Ma, Sean R Landman, Vipin Kumar, Tae Hyun Hwang, Ganesh V Raj, Celestia S Higano, Colm Morrissey, Peter S Nelson, Stephen R Plymate, Scott M Dehm
Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumours...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#16
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892725/investigational-serine-threonine-kinase-inhibitors-against-prostate-cancer-metastases
#17
Claudio Festuccia
INTRODUCTION: Androgen deprivation therapy (ADT) is used as first therapeutic approach in prostate cancer (PCa) although castration resistant disease (CRPC) develops with high frequency. CRPC is the consequence of lack of apoptotic responses to ADT. Alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy were used in CRPC. Serine/threonine protein kinases (STKs) regulate different molecular pathways of normal and neoplastic cells and participate to development of CRPC as well as to the progression towards a bone metastatic disease (mCRPC)...
November 28, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27891324/high-throughput-cell-based-compound-screen-identifies-pinosylvin-methyl-ether-and-tanshinone-iia-as-inhibitors-of-castration-resistant-prostate-cancer
#18
Kirsi Ketola, Miro Viitala, Pekka Kohonen, Vidal Fey, Zoran Culig, Olli Kallioniemi, Kristiina Iljin
Current treatment options for castration-resistant prostate cancer (CRPC) are limited. In this study, a high-throughput screen of 4910 drugs and drug-like molecules was performed to identify antiproliferative compounds in androgen ablated prostate cancer cells. The effect of compounds on cell viability was compared in androgen ablated LNCaP prostate cancer cells and in LNCaP cells grown in presence of androgens as well as in two non-malignant prostate epithelial cells (RWPE-1 and EP156T). Validation experiments of cancer specific anti-proliferative compounds indicated pinosylvin methyl ether (PSME) and tanshinone IIA as potent inhibitors of androgen ablated LNCaP cell proliferation...
March 30, 2016: Journal of Molecular Biochemistry
https://www.readbyqxmd.com/read/27890446/efficacy-of-therapies-after-galeterone-in-patients-with-castration-resistant-prostate-cancer
#19
Rana R McKay, Lillian Werner, Matthew Fiorillo, Jennifer Roberts, Elisabeth I Heath, Glenn J Bubley, Robert Bruce Montgomery, Mary-Ellen Taplin
BACKGROUND: Galeterone is a multi-targeted agent with activity as a CYP17 inhibitor, androgen receptor antagonist, and also causes androgen receptor degradation. It has shown meaningful anti-tumor activity with a well-tolerated safety profile in patients with castration-resistant prostate cancer (CRPC) in phase I and II studies; however, the efficacy of currently approved CRPC therapies after treatment with galeterone is unknown. In this study, we evaluate prostate specific antigen (PSA) response of non-protocol therapies following galeterone in a subset of patients treated on the Androgen Receptor Modulation Optimized for Response (ARMOR) 2 study...
October 27, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27889882/true-incidence-of-gleason-6-pathology-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc
#20
Alena Böker, Markus A Kuczyk, Mario W Kramer, Axel S Merseburger, Katharina Krüger, Florian Imkamp, Christoph A von Klot
INTRODUCTION: Recent evidence from histology studies regarding random prostate biopsies hint toward a relationship between higher biopsy Gleason score and the development of metastatic castration resistant prostate cancer (mCRPC). However, prostate biopsy underestimates final pathology in about one-third of patients. We evaluated the final whole gland pathology from radical prostatectomy exclusively in order to assess the true risk of progressing to the mCRPC state for patients with confirmed Gleason ≤6 prostate cancer...
November 26, 2016: Advances in Therapy
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