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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
#1
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
#2
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/27903350/-effect-of-lumbar-dorsal-muscle-injuries-on-lumbar-vertebral-bone-quality-of-rat
#3
X P Wang, S J Wang, P Yan, L L Zhu, M Q Li, Z Y Bian, J W Tian
Objective: To explored the effects of lumbar dorsal muscle damage on local lumbar vertebral bone quality. Methods: Thirty SD female rats, at age of 20 weeks, were randomly divided into three groups: control group, or say pseudo surgery group, an incision in the back were performed as CNT; bilateral erector spinal muscle group in which group bilateral lumbar erector spinal muscle were removed as RESM; castration group in which bilateral ovaries were resected as OVX.After three months, bone mineral density, microscopic CT and vertebral compression test were taken in lumbar vertebral (L4-6) in turn...
November 22, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27900064/enzalutamide-induced-acute-generalized-exanthematous-pustulosis
#4
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
#5
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
#6
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/27896639/seom-clinical-guideline-for-bone-metastases-from-solid-tumours-2016
#7
C Grávalos, C Rodríguez, A Sabino, M Á Seguí, J A Virizuela, A Carmona, J Cassinello, D Isla, C Jara, M Martín
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease...
November 28, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27896270/the-assessment-of-facial-expressions-in-piglets-undergoing-tail-docking-and-castration-toward-the-development-of-the-piglet-grimace-scale
#8
Pierpaolo Di Giminiani, Victoria L M H Brierley, Annalisa Scollo, Flaviana Gottardo, Emma M Malcolm, Sandra A Edwards, Matthew C Leach
Many piglets are exposed to potentially painful husbandry procedures within the first week of life, including tail docking and castration, without the provision of either anesthesia or analgesia. The assessment methods used to evaluate pain experienced by piglets are often affected by low specificity and practical limitations, prompting the investigation of alternative methodologies. The assessment of changes in facial expression following a painful event has been successfully applied to several species. The objective of this pilot study was to evaluate the utility of a Grimace Scale applied to neonatal pigs to evaluate pain evoked by tail docking and castration...
2016: Frontiers in Veterinary Science
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27888773/the-combined-effects-of-grain-supplementation-and-tenderstretching-on-alpaca-vicugna-pacos-meat-quality
#14
M A Smith, R D Bush, R J van de Ven, D L Hopkins
This study investigated the effects of feeding a mixed grain supplement and tenderstretching (TS) alpaca carcasses on meat quality. A total of 56 castrated 24month old alpacas were divided into two treatments (pasture-only, and pasture plus supplementation). Supplemented groups were fed a mixed grain ration in addition to ad lib pasture for 10weeks. Animals were slaughtered across two kill days (n=28). One half of each carcass was suspended by the pelvis (TS) prior to chilling, and the other half was Achilles tendon hung (AH)...
November 21, 2016: Meat Science
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#15
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
November 24, 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27883295/identification-of-novel-snps-associated-with-risk-and-prognosis-in-patients-with-castration-resistant-prostate-cancer
#16
Tristan M Sissung, John Deeken, Crystal R Leibrand, Douglas K Price, Sheryl Ehrlich, Seth M Steinberg, David J Liewehr, William Dahut, William D Figg
AIM: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). MATERIALS & METHODS: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. RESULTS: No relation to risk was found...
November 24, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27879971/tcr-diversity-a-universal-cancer-immunotherapy-biomarker
#17
EDITORIAL
Douglas G McNeel
Sipuleucel-T was approved as a treatment for men with advanced metastatic, castration-resistant prostate cancer on the basis of improved survival in randomized clinical trials. A major challenge for this therapy, as well as other newer cancer immunotherapy agents, has been to identify markers that can identify patients who benefit from these therapies. In a recent manuscript by Sheikh and colleagues, the investigators evaluated changes in T cell clonality in the peripheral blood and tumors of patients treated with sipuleucel-T using next generation sequencing of T cell receptor Vß CDR3 sequences...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27878919/effect-of-health-status-on-fattening-performance-in-young-crossbred-polish-holstein-friesian-%C3%A3-limousin-bulls-and-steers
#18
Zofia Wielgosz-Groth, Monika Sobczuk-Szul, Zenon Nogalski, Paulina Pogorzelska-Przybyłek, Cezary Purwin
The aim of this study was to determine the effect of disease incidence on selected parameters of cattle fattening performance and carcass quality, and the fatty acid profile of beef. The experimental materials comprised 16 bulls and 16 steers, Polish Holstein-Friesian × Limousin crossbreeds (including 10 healthy and six treated animals of each category). At 5 weeks of age, bloodless castration was carried out using a rubber elastrator. The calves were fed milk replacer provided in automatic feeding stations...
November 23, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/27878410/the-sexual-orientation-and-gender-presentation-of-hijra-kothi-and-panthi-in-mumbai-india
#19
Matthew Stief
Cultural categories related to sexuality and gender vary considerably cross-culturally. While Western cultures categorize people primarily in terms of sexual attractions (i.e., gay, straight, bisexual), many cultures distinguish between groups based on additional issues such as gender role presentation and position preference in anal sex (i.e., insertive/receptive). The current study gathered data on three categories of natal males in Mumbai, India-hijra, kothi, and panthi (N = 93). Hijra are androphilic (sexually attracted to adult men), typically sexually receptive, transgender, sometimes castrated, and live in fictive kinship networks that are hierarchically organized...
November 22, 2016: Archives of Sexual Behavior
https://www.readbyqxmd.com/read/27878318/-corticosteroids-in-the-management-of-advanced-prostate-cancer
#20
H Kübler
Corticosteroids have been widely used for decades in cancer therapy, predominantly due to their anti-inflammatory activity. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), corticosteroids play an important role both in the management of tumor-related symptoms, especially bone metastasis-related pain, and as concomitant treatment to counteract side effects associated with approved active prostatic anticancer agents such as docetaxel, cabazitaxel, and abiraterone acetate. In association with abiraterone acetate, low-dose corticosteroids (prednisone or prednisolone) reduce the mineralocorticoid side effects of abiraterone...
November 22, 2016: Der Urologe. Ausg. A
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