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https://www.readbyqxmd.com/read/28816284/-predictive-factor-analysis-of-time-to-progression-of-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy
#1
G J Ji, C Huang, G Song, X S Li, Y Song, L Q Zhou
OBJECTIVE: To explore risk factors including prostate-specific antigen (PSA) kinetics for the prediction of castration-resistant prostate cancer (CRPC), and to build a practical model for predicting the progression to CRPC after androgen deprivation therapy (ADT) so as to facilitate clinicians in decision-making for prostate cancer patients receiving ADT. METHODS: A total of 185 patients with prostate cancer who had received ADT as the primary therapy in Department of Urology of Peking University First Hospital from 2003 to 2014 were enrolled retrospectively...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28757136/iminoenamine-based-novel-androgen-receptor-antagonist-exhibited-anti-prostate-cancer-activity-in-androgen-independent-prostate-cancer-cells-through-inhibition-of-akt-pathway
#2
S Divakar, K Saravanan, P Karthikeyan, R Elancheran, S Kabilan, K K Balasubramanian, Rajlakshmi Devi, J Kotoky, M Ramanathan
Treatment by androgen receptor (AR) antagonists is one of the regimens for prostate cancer. The prolonged treatment with AR antagonist leads to the expression of point mutation in the ligand binding domain of the AR. This point mutation causes resistance to AR antagonist by converting them into an agonist. The T887A mutated AR was frequently expressed in androgen independent prostate cancer (AIPC) patients. Through literature survey and molecular modelling, we have identified a novel AR antagonist having a bulky β-iminoenamine BF2 complex scaffold...
July 27, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28745319/the-androgen-receptor-is-a-negative-regulator-of-eif4e-phosphorylation-at-s209-implications-for-the-use-of-mtor-inhibitors-in-advanced-prostate-cancer
#3
L S D'Abronzo, S Bose, M E Crapuchettes, R E Beggs, R L Vinall, C G Tepper, S Siddiqui, M Mudryj, F U Melgoza, B P Durbin-Johnson, R W deVere White, P M Ghosh
The antiandrogen bicalutamide is widely used in the treatment of advanced prostate cancer (PCa) in many countries, but its effect on castration-resistant PCa (CRPC) is limited. We previously showed that resistance to bicalutamide results from activation of mechanistic target of rapamycin (mTOR). Interestingly, clinical trials testing combinations of the mTOR inhibitor RAD001 with bicalutamide were effective in bicalutamide-naïve CRPC patients, but not in bicalutamide-pretreated ones. Here we investigate causes for their difference in response...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28743076/lc-ms-ms-esi-method-for-simultaneous-quantification-of-darolutamide-and-its-active-metabolite-orm-15341-in-mice-plasma-and-its-application-to-a-pharmacokinetic-study
#4
Sreekanth Dittakavi, Pavan Kumar V S P Nagasuri, Suresh P Sulochana, Syed Mohd Saim, Sadanand R Mallurwar, Mohd Zainuddin, Purushottam Dewang, Sriram Rajagopal, Ramesh Mullangi
A sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous quantitation of darolutamide and its active metabolite i.e. ORM-15341 in 50μL mice plasma using bicalutamide as an internal standard (I.S.) as per regulatory guidelines. Sample processing was accomplished through liquid-liquid extraction. Chromatographic separation was achieved using an Atlantis C18 column with an isocratic mobile phase comprising 0.2% formic acid:acetonitrile (35:65, v/v) at a flow rate of 0.8mL/min within 2...
July 13, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28734596/developments-in-urologic-oncology-%C3%A2-oncoforum%C3%A2-the-best-of-2016
#5
F Gómez-Veiga, A Alcaraz-Asensio, J Burgos-Revilla, J M Cózar-Olmo
OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2016 in the main annual meetings. ACQUISITION OF EVIDENCE: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. SYNTHESIS OF EVIDENCE: In High-Risk Renal-Cell carcinoma after nephrectomy, disease-free survival was significantly greater for sunitinib than placebo group, with adverse events more frequents...
July 19, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28716370/a-systematic-review-and-framework-for-the-use-of-hormone-therapy-with-salvage-radiation-therapy-for-recurrent-prostate-cancer
#6
REVIEW
Daniel E Spratt, Robert T Dess, Zachary S Zumsteg, Daniel W Lin, Phuoc T Tran, Todd M Morgan, Emmanuel S Antonarakis, Paul L Nguyen, Charles J Ryan, Howard M Sandler, Matthew R Cooperberg, Edwin Posadas, Felix Y Feng
CONTEXT: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. OBJECTIVE: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. EVIDENCE ACQUISITION: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials...
July 14, 2017: European Urology
https://www.readbyqxmd.com/read/28704421/transcriptional-role-of-androgen-receptor-in-the-expression-of-long-non-coding-rna-sox2ot-in-neurogenesis
#7
Valentina Tosetti, Jenny Sassone, Anna L M Ferri, Michela Taiana, Gloria Bedini, Sara Nava, Greta Brenna, Chiara Di Resta, Davide Pareyson, Anna Maria Di Giulio, Stephana Carelli, Eugenio A Parati, Alfredo Gorio
The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined...
2017: PloS One
https://www.readbyqxmd.com/read/28698198/abcb1-mediates-cabazitaxel-docetaxel-cross-resistance-in-advanced-prostate-cancer
#8
Alan P Lombard, Chengfei Liu, Cameron M Armstrong, Vito Cucchiara, Xinwei Gu, Wei Lou, Christopher P Evans, Allen C Gao
in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood...
July 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28672724/anticancer-drugs-in-portuguese-surface-waters-estimation-of-concentrations-and-identification-of-potentially-priority-drugs
#9
Mónica S F Santos, Helena Franquet-Griell, Silvia Lacorte, Luis M Madeira, Arminda Alves
Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28666849/the-indications-of-tautomeric-conversion-in-amorphous-bicalutamide-drug
#10
Marzena Rams-Baron, Patryk Wlodarczyk, Mateusz Dulski, Agnieszka Wlodarczyk, Danuta Kruk, Adam Rachocki, Renata Jachowicz, Marian Paluch
No abstract text is available yet for this article.
June 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28660504/distribution-of-six-anticancer-drugs-and-a-variety-of-other-pharmaceuticals-and-their-sorption-onto-sediments-in-an-urban-japanese-river
#11
Takashi Azuma, Natsumi Arima, Ai Tsukada, Satoru Hirami, Rie Matsuoka, Ryogo Moriwake, Hirotaka Ishiuchi, Tomomi Inoyama, Yusuke Teranishi, Misato Yamaoka, Mao Ishida, Kanae Hisamatsu, Ayami Yunoki, Yoshiki Mino
The distributions of 31 pharmaceuticals grouped into nine therapeutic classes, including six anticancer drugs, were investigated in the waters and sediments of an urban river in Japan. The coefficients of sorption (logK d) to the river sediments were also determined from the results of a field survey and laboratory-scale experiment. Three anticancer drugs-bicalutamide, doxifluridine, and tamoxifen-were detected in the river sediments at maximum concentrations of 391, 392, and 250 ng/kg, respectively. In addition, the transformation products of psychotropic carbamazepine (2-hydroxy carbamazepine, acridine, and acridone) were detected in the range of 108 ng/kg (2-hydroxy carbamazepine) to 2365 ng/kg (acridine), and the phytoestrogen glycitein was detected in the range of N...
June 28, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28645652/androgen-inhibits-key-atherosclerotic-processes-by-directly-activating-adtrp-transcription
#12
Chunyan Luo, Elisabeth Pook, Bo Tang, Weiyi Zhang, Sisi Li, Kirsten Leineweber, Shing-Hu Cheung, Qiuyun Chen, Martin Bechem, Jing-Shan Hu, Volker Laux, Qing Kenneth Wang
Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. In this study, we identified the molecular mechanism by which androgen regulates ADTRP expression and tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642838/adaptive-pathways-and-emerging-strategies-overcoming-treatment-resistance-in-castration-resistant-prostate-cancer
#13
Cameron M Armstrong, Allen C Gao
The therapies available for prostate cancer patients whom progress from hormone-sensitive to castration resistant prostate cancer include both systemic drugs, including docetaxel and cabazitaxel, and drugs that inhibit androgen signaling such as enzalutamide and abiraterone. Unfortunately, it is estimated that up to 30% of patients have primary resistance to these treatments and over time even those who initially respond to therapy will eventually develop resistance and their disease will continue to progress regardless of the presence of the drug...
October 2016: Asian Journal of Urology
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#14
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28626511/assessment-of-real-world-central-nervous-system-events-in-patients-with-advanced-prostate-cancer-using-abiraterone-acetate-bicalutamide-enzalutamide-or-chemotherapy
#15
Dominic Pilon, Ajay S Behl, Lorie A Ellis, Marie-Noëlle Robitaille, Patrick Lefebvre, Nancy A Dawson
BACKGROUND: Central nervous system (CNS) events are frequently reported among patients with advanced prostate cancer as a consequence of the treatments used in this patient population. OBJECTIVE: To assess the incidence of CNS events in patients with advanced prostate cancer who initiated treatment with abiraterone acetate, bicalutamide, enzalutamide, or chemotherapy. METHODS: The Truven Health MarketScan Research databases were used to retrospectively identify patients with prostate cancer who initiated treatment with abiraterone acetate, enzalutamide, bicalutamide, or chemotherapy after September 1, 2012 (ie, the index date)...
May 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28607007/synergistic-activity-with-notch-inhibition-and-androgen-ablation-in-erg-positive-prostate-cancer-cells
#16
Ahmed A Mohamed, Shyh-Han Tan, Charles P Xavier, Shilpa Katta, Wei Huang, Lakshmi Ravindranath, Muhammad Jamal, Hua Li, Meera Srivastava, Eri S Srivatsan, Taduru L Sreenath, David G McLeod, Alagarsamy Srinivasan, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava
The oncogenic activation of the ETS related gene (ERG) due to gene fusions is present in over half of prostate cancer (CaP) in Western countries. Due to its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for CaP. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified; confirming that NOTCH factors are direct transcriptional targets of ERG...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28571783/improving-the-physicochemical-properties-of-bicalutamide-by-complex-formation-with-bovine-serum-albumin
#17
Congbin Yang, Peiwen Di, JinPing Fu, Hui Xiong, Qiufang Jing, Guobin Ren, Yun Tang, Wenyun Zheng, Guixia Liu, Fuzheng Ren
Bicalutamide-bovine serum albumin (Bic-BSA) complexes were prepared by anti-solvent precipitation. Bovine serum albumin (BSA) was used as a stabilizer for particle growth. The physicochemical properties of Bic-BSA were analyzed by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. The interaction between Bic and BSA was characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, fluorescence spectroscopy and molecular docking. The particle size could be easily reduced to 1-10μm with a good lognormal distribution...
August 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28562322/characterization-of-a-novel-androgen-receptor-ar-coregulator-ripk1-and-related-chemicals-that-suppress-ar-mediated-prostate-cancer-growth-via-peptide-and-chemical-screening
#18
Cheng-Lung Hsu, Jai-Shin Liu, Ting-Wei Lin, Ying-Hsu Chang, Yung-Chia Kuo, An-Chi Lin, Huei-Ju Ting, See-Tong Pang, Li-Yu Lee, Wen-Lung Ma, Chun-Cheng Lin, Wen-Guey Wu
Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28562037/computational-discovery-and-experimental-validation-of-inhibitors-of-the-human-intestinal-transporter-oatp2b1
#19
Natalia Khuri, Arik A Zur, Matthias B Wittwer, Lawrence Lin, Sook Wah Yee, Andrej Sali, Kathleen M Giacomini
Human organic anion transporters (OATPs) are vital for the uptake and efflux of drugs and endogenous compounds. Current identification of inhibitors of these transporters is based on experimental screening. Virtual screening remains a challenge due to a lack of experimental three-dimensional protein structures. Here, we describe a workflow to identify inhibitors of the OATP2B1 transporter in the DrugBank library of over 5,000 drugs and druglike molecules. OATP member 2B1 transporter is highly expressed in the intestine, where it participates in oral absorption of drugs...
June 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28552710/clinical-outcomes-and-testosterone-levels-following-continuous-androgen-deprivation-in-patients-with-relapsing-or-locally-advanced-prostate-cancer-a-post-hoc-analysis-of-the-iceland-study
#20
Bertrand Tombal, Erik B Cornel, Raj Persad, Anny Stari, Francisco Gómez Veiga, Claude Schulman
PURPOSE: Lower serum testosterone levels correlate with improved cause-specific survival and longer time to progression in the first year of continuous androgen deprivation in men with prostate cancer. ICELAND was a large, European study demonstrating the efficacy of leuprorelin (Eligard(®)) during continuous androgen deprivation. This post hoc analysis investigated serum testosterone levels within the first year of continuous androgen deprivation for survival and time to progression...
May 25, 2017: Journal of Urology
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