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https://www.readbyqxmd.com/read/28741687/a-distinct-plasma-lipid-signature-associated-with-poor-prognosis-in-castration-resistant-prostate-cancer-authors
#1
H-M Lin, K L Mahon, J M Weir, P A Mundra, C Spielman, K Briscoe, H Gurney, G Mallesara, G Marx, M R Stockler, PRIMe Consortium, R G Parton, A J Hoy, R J Daly, P J Meikle, L G Horvath
Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28739142/radiation-therapy-for-oligorecurrence-in-prostate-cancer-preliminary-results-of-our-centre
#2
C González Ruiz de León, M Ramírez Backhaus, M Sobrón Bustamante, J Casaña, L Arribas, J Rubio-Briones
INTRODUCTION AND OBJECTIVE: There is growing interest in the use of more aggressive therapeutic modalities for treating metastatic prostate cancer. In this study, we examine the use of stereotactic body radiation therapy (SBRT) for patients with oligorecurrent prostate cancer. We analysed the biochemical response and toxicity of patients who underwent this therapy at our centre. MATERIAL AND METHOD: We selected patients who experienced oligorecurrence between January 2015 to December 2016 and were administered SBRT...
July 21, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28736322/clinical-outcomes-of-chemotherapy-na%C3%A3-ve-men-with-metastatic-castration-resistant-prostate-cancer-and-low-baseline-psa-treated-with-enzalutamide-vs-placebo
#3
Mary-Ellen Taplin, Andrew J Armstrong, Ping Lin, Andrew Krivoshik, De Phung, Teresa Parli, Bertrand Tombal, Tomasz M Beer
PURPOSE: Metastatic castration-resistant prostate cancer with low baseline prostate-specific antigen represents an early stage in the natural history of castration-resistant prostate cancer disease progression (low-volume disease), low prostate-specific antigen-producing disease, or disease less dependent on androgen receptor biology (high-volume disease). We analyzed outcomes in men with low prostate-specific antigen and high disease burden who received the oral androgen-receptor inhibitor enzalutamide in the PREVAIL study...
July 20, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28736082/differential-proteome-expression-analysis-of-androgen-dependent-and-independent-pathways-in-lncap-prostate-cancer-cells
#4
Seho Cha, Dong Hoon Shin, Jun Ryeong Seok, Jae Kyung Myung
Prostate cancer (PC) is one of the leading causes of cancer death in men. It commonly develops in older males, but the number of younger men diagnosed with the disease has increased in recent years. Hormone therapies, such as chemical and surgical methods that inhibit androgen synthesis or androgen receptor (AR) activation, have been used for advanced disease. However, castration-resistant PC (CRPC), which exhibits androgen-independent mechanisms for activating AR, develops after a few years of such treatment and no therapy is available...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#5
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734596/developments-in-urologic-oncology-%C3%A2-oncoforum%C3%A2-the-best-of-2016
#6
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/28733443/direct-metabolic-interrogation-of-dihydrotestosterone-biosynthesis-from-adrenal-precursors-in-primary-prostatectomy-tissues
#7
Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J Stephenson, Eric A Klein, Nima Sharifi
Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28730293/clinical-predictors-of-survival-in-patients-with-castration-resistant-prostate-cancer-receiving-sipuleucel-t-cellular-immunotherapy
#8
Mehmet Asim Bilen, Kenneth R Hess, Sumit K Subudhi, Ana Aparicio, Jeri Kim, Amado J Zurita-Saavedra, John C Araujo, Paul G Corn, Jessica Stover, Sue-Hwa Lin, Christopher J Logothetis, Shi-Ming Tu
BACKGROUND: We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T. METHODS: We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model...
July 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28729398/quercetin-targets-hnrnpa1-to-overcome-enzalutamide-resistance-in-prostate-cancer-cells
#9
Ramakumar Tummala, Wei Lou, Allen C Gao, Nagalakshmi Nadiminty
Prostate cancer remains dependent on androgen receptor signaling even after castration. Aberrant androgen receptor signaling in castration resistant prostate cancer is mediated by mechanisms such as alterations in the androgen receptor and activation of interacting signaling pathways. Clinical evidence confirms that resistance to the next generation anti-androgen, enzalutamide, may be mediated to a large extent by alternative splicing of the androgen receptor to generate constitutively active splice variants such as AR-V7...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729067/real-world-characteristics-and-outcomes-of-patients-with-metastatic-castration-resistant-prostate-cancer-receiving-chemotherapy-versus-androgen-receptor-targeted-therapy-after-failure-of-first-line-androgen-receptor-targeted-therapy-in-the-community-setting
#10
William K Oh, Raymond Miao, Francis Vekeman, Jennifer Sung, Wendy Y Cheng, Marjolaine Gauthier-Loiselle, Ravinder Dhawan, Mei Sheng Duh
BACKGROUND: In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices. PATIENTS AND METHODS: Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation...
June 19, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28725594/weekly-ascorbic-acid-infusion-in-castration-resistant-prostate-cancer-patients-a-single-arm-phase-ii-trial
#11
Torben K Nielsen, Martin Højgaard, Jon T Andersen, Niklas Rye Jørgensen, Bo Zerahn, Bent Kristensen, Trine Henriksen, Jens Lykkesfeldt, Kári J Mikines, Henrik E Poulsen
BACKGROUND: Ascorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment. METHODS: This non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28724986/core-shell-lipid-polymer-hybrid-nanoparticles-with-combined-docetaxel-and-molecular-targeted-therapy-for-the-treatment-of-metastatic-prostate-cancer
#12
Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724614/nuclear-mtor-acts-as-a-transcriptional-integrator-of-the-androgen-signaling-pathway-in-prostate-cancer
#13
Étienne Audet-Walsh, Catherine R Dufour, Tracey Yee, Fatima Z Zouanat, Ming Yan, Georges Kalloghlian, Mathieu Vernier, Maxime Caron, Guillaume Bourque, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Armen G Aprikian, Jacques Lapointe, Simone Chevalier, Vincent Giguère
Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#14
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723523/metastatic-castration-resistant-prostate-cancer-major-progress-leading-to-even-more-questions
#15
Nicolas Mottet
Treatment of metastatic castration-resistant prostate cancer is complex and we are facing more questions with major practical impact with the available effective drugs. Treatment optimization requires that all clinical partners work together. Survival is linked to the number of regimen used. The androgen pathway is key, while chemotherapy is the other major tool.
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723521/bone-scan-index-and-progression-free-survival-data-for-progressive-metastatic-castration-resistant-prostate-cancer-patients-who-received-odm-201-in-the-arades-multicentre-study
#16
Mariana Reza, Robert Jones, John Aspegren, Christophe Massard, Leena Mattila, Mika Mustonen, Per Wollmer, Elin Trägårdh, Eva Bondesson, Lars Edenbrandt, Karim Fizazi, Anders Bjartell
BACKGROUND: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. OBJECTIVE: To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723520/bone-scan-index-as-an-imaging-biomarker-in-metastatic-castration-resistant-prostate-cancer-a-multicentre-study-based-on-patients-treated-with-abiraterone-acetate-zytiga-in-clinical-practice
#17
Mariana Reza, Mattias Ohlsson, Reza Kaboteh, Aseem Anand, Ingela Franck-Lissbrant, Jan-Erik Damber, Anders Widmark, Camilla Thellenberg-Karlsson, Lars Budäus, Thomas Steuber, Till Eichenauer, Per Wollmer, Lars Edenbrandt, Elin Trägårdh, Anders Bjartell
BACKGROUND: Abiraterone acetate (AA) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. To measure treatment response accurately in bone, quantitative methods are needed. The Bone Scan Index (BSI), a prognostic imaging biomarker, reflects the tumour burden in bone as a percentage of the total skeletal mass calculated from bone scintigraphy. OBJECTIVE: To evaluate the value of BSI as a biomarker for outcome evaluation in mCRPC patients on treatment with AA according to clinical routine...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723519/individual-patient-data-analysis-of-randomized-clinical-trials-impact-of-black-race-on-castration-resistant-prostate-cancer-outcomes
#18
Daniel E Spratt, Yu-Wei Chen, Brandon A Mahal, Joseph R Osborne, Shuang G Zhao, Todd M Morgan, Ganesh Palapattu, Felix Y Feng, Paul L Nguyen
BACKGROUND: Population data suggest that black men have a higher risk of dying from prostate cancer (PCa) than other racial ethnicities. OBJECTIVE: To examine the impact of black race on progression-free survival (PFS) and overall survival (OS) among men with metastatic castration-resistant PCa (mCRPC) enrolled in randomized controlled trials (RCTs). DESIGN, SETTING, AND PARTICIPANTS: A pooled analysis was performed on individual patient data from five modern PCa RCTs available from Project Data Sphere...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723518/mid-term-outcomes-following-salvage-lymph-node-dissection-for-prostate-cancer-nodal-recurrence-status-post-radical-prostatectomy
#19
Fabio Zattoni, Avinash Nehra, Christopher R Murphy, Laureano Rangel, Lance Mynderse, Val Lowe, Eugene Kwon, R Jeffrey Karnes
BACKGROUND: Patients with oligometastatic prostate cancer lymph node recurrence can be treated with many options including salvage lymph node dissection (sLND). OBJECTIVE: Evaluation of outcomes of sLND and identification of clinicopathologic features in predicting further biochemical and radiological relapse after sLND for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Between November 1, 2009 and March 31, 2015, 117 patients with biochemical recurrence (BCR) after radical prostatectomy (RP) underwent sLND by a single surgeon after a standardized 11C-choline positron emission tomography/computed tomography...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723516/the-molecular-evolution-of-castration-resistant-prostate-cancer
#20
REVIEW
Yvonne Ceder, Anders Bjartell, Zoran Culig, Mark A Rubin, Scott Tomlins, Tapio Visakorpi
CONTEXT: Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. However, castration-resistant prostate cancer (CRPC) nearly invariably develops through a range of different molecular mechanisms accompanied by progression to a more aggressive phenotype. OBJECTIVE: To understand the key molecular mechanisms leading to CRPC and the functional implications of this progression. Understanding molecular evolutionary mechanisms in CRPC is essential for the development of novel curative therapeutic approaches...
December 2016: European Urology Focus
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