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https://www.readbyqxmd.com/read/28077788/androgen-receptor-splice-variants-and-prostate-cancer-from-bench-to-bedside
#1
REVIEW
Kristine M Wadosky, Shahriar Koochekpour
Therapeutic interventions for advanced prostate cancer (PCa) center on inhibiting androgen receptor (AR) and downstream signaling pathways. Resistance to androgen deprivation therapy and/or AR antagonists is inevitable and molecular mechanisms driving castration-resistant PCa (CR-PCa) primarily involve alterations in AR expression and activity. Detailed molecular biology work over the past decade, discussed at length in this review article, has revealed several AR transcripts that result from alternative splicing...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074331/a-retrospective-analysis-of-the-first-41-mcrpc-patients-with-bone-pain-treated-with-radium-223-at-the-national-institute-of-oncology-in-hungary
#2
Zs Küronya, I Sinkovics, P Ágoston, K Bíró, I Bodrogi, I Böde, M Dank, F Gyergyay, T Vajdics, Zs Kolonics, K Nagyiványi, Á Rúzsa, L Géczi
Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records...
January 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28074210/diagnostic-value-of-additional-68-ga-psma-pet-before-223-ra-dichloride-therapy-in-patients-with-metastatic-prostate-carcinoma
#3
Axel Bräuer, Kambiz Rahbar, Julia Konnert, Martin Bögemann, Lars Stegger
PURPOSE: Medical imaging plays an important role in selecting patients with metastatic castration-resistant prostate cancer for (223)Ra-dichloride therapy of bone metastases. The purpose of this study was to investigate whether (68)Ga-PSMA-PET has incremental value over conventional imaging for selecting patients suitable for (223)Ra-dichloride therapy. METHODS: In 27 consecutive patients referred for (223)Ra-dichloride therapy additional (68)Ga-PSMA-PET/CT was performed and tracer distribution was evaluated systematically with respect to the detection of visceral metastases and bone metastases with inadequate uptake on bone scintigraphy...
January 11, 2017: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#4
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#5
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
https://www.readbyqxmd.com/read/28068321/analysis-of-dna-methylation-in-single-circulating-tumor-cells
#6
C F Pixberg, K Raba, F Müller, B Behrens, E Honisch, D Niederacher, H Neubauer, T Fehm, W Goering, W A Schulz, P Flohr, G Boysen, M Lambros, J S De Bono, W T Knoefel, C Sproll, N H Stoecklein, R P L Neves
Direct analysis of circulating tumor cells (CTCs) can inform on molecular mechanisms underlying systemic spread. Here we investigated promoter methylation of three genes regulating epithelial-to-mesenchymal transition (EMT), a key mechanism enabling epithelial tumor cells to disseminate and metastasize. For this, we developed a single-cell protocol based on agarose-embedded bisulfite treatment, which allows investigating DNA methylation of multiple loci via a multiplex PCR (multiplexed-scAEBS). We established our assay for the simultaneous analysis of three EMT-associated genes miR-200c/141, miR-200b/a/429 and CDH1 in single cells...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28068151/prognostic-impact-of-pretreatment-neutrophil-to-lymphocyte-ratio-in-castration-resistant-prostate-cancer-patients-treated-with-first-line-docetaxel
#7
Consuelo Buttigliero, Chiara Pisano, Marcello Tucci, Francesca Vignani, Valentina Bertaglia, Davide Iaconis, Pamela Guglielmini, Gianmauro Numico, Giorgio V Scagliotti, Massimo Di Maio
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammatory response, has been associated with poor outcome in several solid tumors, including prostate cancer. We retrospectively investigated the prognostic role of pretreatment NLR in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel. METHODS: All CRPC patients treated with first-line docetaxel at two Italian institutions, with available data about baseline neutrophil and lymphocyte values, were included in this retrospective analysis...
January 9, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28067867/germline-brca2-mutations-drive-prostate-cancers-with-distinct-evolutionary-trajectories
#8
Renea A Taylor, Michael Fraser, Julie Livingstone, Shadrielle Melijah G Espiritu, Heather Thorne, Vincent Huang, Winnie Lo, Yu-Jia Shiah, Takafumi N Yamaguchi, Ania Sliwinski, Sheri Horsburgh, Alice Meng, Lawrence E Heisler, Nancy Yu, Fouad Yousif, Melissa Papargiris, Mitchell G Lawrence, Lee Timms, Declan G Murphy, Mark Frydenberg, Julia F Hopkins, Damien Bolton, David Clouston, John D McPherson, Theodorus van der Kwast, Paul C Boutros, Gail P Risbridger, Robert G Bristow
Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC)...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28063845/comparative-assessment-of-efficacies-between-2%C3%A2-alternative-therapeutic-sequences-with-novel%C3%A2-androgen-receptor-axis-targeted-agents%C3%A2-in-patients-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#9
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28063195/first-line-non-cytotoxic-therapy-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-a-systematic-review-of-ten-randomised-clinical-trials
#10
REVIEW
Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke
OBJECTIVE: To systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We systematically searched PubMed, EMBASE, and the Cochrane libraries up to March 1, 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated...
January 6, 2017: BJU International
https://www.readbyqxmd.com/read/28062857/positive-feedback-loop-mediated-by-protein-phosphatase-1%C3%AE-mobilization-of-p-tefb-and-basal-cdk1-drives-androgen-receptor-in-prostate-cancer
#11
Xiaming Liu, Yanfei Gao, HuiHui Ye, Sean Gerrin, Fen Ma, Yiming Wu, Tengfei Zhang, Joshua Russo, Changmeng Cai, Xin Yuan, Jihong Liu, Shaoyong Chen, Steven P Balk
P-TEFb (CDK9/cyclin T) plays a central role in androgen receptor (AR)-mediated transactivation by phosphorylating both RNA polymerase 2 complex proteins and AR at S81. CDK9 dephosphorylation mobilizes P-TEFb from an inhibitory 7SK ribonucleoprotein complex, but mechanisms targeting phosphatases to P-TEFb are unclear. We show that AR recruits protein phosphatase 1α (PP1α), resulting in P-TEFb mobilization and CDK9-mediated AR S81 phosphorylation. This increased pS81 enhances p300 recruitment, histone acetylation, BRD4 binding and subsequent further recruitment of P-TEFb, generating a positive feedback loop that sustains transcription...
January 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28058455/-bone-specific-therapy-with-radium-223-dichloride-castration-resistant-prostate-cancer-with-symptomatic-bone-metastases
#12
R Tauber, J Gschwend, K Scheidhauer, M Eiber, M Krönke
Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment...
January 5, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28053513/metastatic-castration-resistant-prostate-cancer-in-very-elderly-patients-challenges-and-solutions
#13
REVIEW
Orazio Caffo, Francesca Maines, Mimma Rizzo, Stefania Kinspergher, Antonello Veccia
The treatment of elderly patients with cancer is usually viewed by clinicians as a challenge, because of the age-related decline in normal organ function and the frequent concomitant administration of multiple drugs for comorbid conditions. Clinicians therefore tend not to prescribe antineoplastic agents (mainly in the case of chemotherapy) to elderly patients, with the fear of excess toxicity leading to an unfavorable cost:benefit ratio. The cutoff age defining a cancer patient as elderly is usually 70 years, but over the last 10 years clinicians have paid more attention to functional status, as evaluated by means of a comprehensive geriatric assessment and comorbidity burden, rather than chronological age...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28049163/correction-niclosamide-inhibits-androgen-receptor-variants-expression-and-overcomes-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#14
(no author information available yet)
No abstract text is available yet for this article.
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28048765/su-f-t-57-delivered-activity-accuracy-of-radium-223-dichloride-injections-when-being-administrated-for-castration-resistant-prostate-cancer-symptomatic-bone-metastases-the-impact-of-residual-activity-in-the-spent-syringe-and-dispensing-accuracy-of-ra-223
#15
G Jennings
PURPOSE: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration - resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. METHODS: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048576/we-h-207a-04-impact-of-lesion-location-on-the-repeatability-of-18f-naf-pet-ct
#16
C Lin, T Perk, S Harmon, S Perlman, G Liu, R Jeraj
PURPOSE: Quantifying the repeatability of imaging biomarkers is critical for assessing therapeutic response. While (18) F-NaF PET/CT has shown to be a repeatable imaging method, research has not shown which factors may influence its repeatability. The purpose of this study was to evaluate whether the location of the lesion impacts the repeatability of quantitative (18) F-NaF PET-derived SUV metrics. METHODS: Metastatic castrate-resistant prostate cancer patients with multiple bone lesions received whole-body test-retest NaF PET/CT scans...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047654/mo-ab-bra-05-18f-naf-pet-ct-imaging-biomarkers-in-metastatic-prostate-cancer
#17
S Harmon, T Perk, C Lin, J Eickhoff, P Choyke, W Dahut, A Apolo, J Humm, S Larson, M J Morris, S Perlman, G Liu, R Jeraj
PURPOSE: Clinical use of (18) F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. METHODS: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047036/we-fg-202-05-quantification-of-bone-flare-on-f-18-naf-pet-ct-in-metastatic-prostate-cancer
#18
A Weisman, S Harmon, T Perk, M Scarpelli, G Liu, R Jeraj
PURPOSE: Bone flare has been observed on Tc-99m bone scans during early assessment in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients receiving select androgen-signaling pathway (AR) targeted treatments, including CYP17-inhibitor Abiraterone. This study investigates the appearance and potential clinical impact of bone flare in mCRPC patients receiving CYP17-inhibitors using (18) F-NaF PET/CT. METHODS: Twenty-three mCRPC patients being treated with CYP17-inhibitors received NaF PET/CT scans at baseline, week 6, and week 12 of treatment...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045115/skeletal-related-events-significantly-impact-health-related-quality-of-life-in-metastatic-castration-resistant-prostate-cancer-data-from-prevail-and-affirm-trials
#19
F Saad, C Ivanescu, D Phung, Y Loriot, S Abhyankar, T M Beer, B Tombal, S Holmstrom
BACKGROUND: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. METHODS: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments...
January 3, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28043910/metformin-inhibits-castration-induced-emt-in-prostate-cancer-by-repressing-cox2-pge2-stat3-axis
#20
Dali Tong, Qiuli Liu, Gaolei Liu, Jing Xu, Weihua Lan, Yao Jiang, Hualiang Xiao, Dianzheng Zhang, Jun Jiang
Castration is the standard therapeutic treatment for advanced prostate cancer but with limited benefit due to the profound relapse and metastasis. Activation of inflammatory signaling pathway and initiation of epithelial-mesenchymal transition (EMT) are closely related to drug resistance, tumor relapseas well as metastasis. In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin...
December 30, 2016: Cancer Letters
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