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https://www.readbyqxmd.com/read/28646594/prevalence-and-prognosis-of-low-volume-oligorecurrent-hormone-sensitive-prostate-cancer-amenable-to-lesion-ablative-therapy
#1
Aurélie De Bruycker, Bieke Lambert, Tom Claeys, Louke Delrue, Chamberlain Mbah, Gert De Meerleer, Geert Villeirs, Filip De Vos, Kathia De Man, Karel Decaestecker, Valérie Fonteyne, Nicolaas Lumen, Filip Ameye, Ignace Billiet, Steven Joniau, Friedl Vanhaverbeke, Wim Duthoy, Piet Ost
OBJECTIVES: To describe the anatomical patterns of PCa recurrence following primary therapy and investigate if patients with low-volume disease have a better prognosis as compared to their counterparts. MATERIAL AND METHODS: Patients eligible for a F18-choline PET-CT were entered in a prospective cohort study. Eligible patients had an asymptomatic biochemical recurrence following primary PCa treatment and testosterone levels >50 ng/ml. The number of lesions were counted per scan...
June 24, 2017: BJU International
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#2
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#3
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641312/impact-of-novel-mir-145-3p-regulatory-networks-on-survival-in-patients-with-castration-resistant-prostate-cancer
#4
Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC)...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#5
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
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
#6
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/28633425/androgen-receptor-mutations-in-patients-with-castration-resistant-prostate-cancer-treated-with-apalutamide
#7
D E Rathkopf, M R Smith, C J Ryan, W R Berry, N D Shore, G Liu, C S Higano, J J Alumkal, R Hauke, R F Tutrone, M Saleh, E Chow Maneval, S Thomas, D S Ricci, M K Yu, C J de Boer, A Trinh, T Kheoh, R Bandekar, H I Scher, E S Antonarakis
Background: : Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. Patients and methods: : Blood samples from men with non-metastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28631436/characterization-of-a-novel-p110%C3%AE-specific-inhibitor-bl140-that-overcomes-mdv3100-resistance-in-castration-resistant-prostate-cancer-cells
#8
Chenchen He, Shaofeng Duan, Liang Dong, Yifen Wang, Qingting Hu, Chunjing Liu, Marcus L Forrest, Jeffrey M Holzbeierlein, Suxia Han, Benyi Li
BACKGROUND: Our previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs. To improve TGX221's aqueous solubility, in this study, we characterized four recently synthesized TGX221 analogs. METHODS: TGX221 analog efficacy were examined in multiple prostate cancer cell lines with the SRB cell growth assay, Western blot assay for AKT phosphorylation and cell cycle protein levels...
June 20, 2017: Prostate
https://www.readbyqxmd.com/read/28614882/-review-on-quality-of-life-in-crpc-patients
#9
Kurt Miller
Health-related quality of life (HRQoL) deteriorates rapidly in patients with advanced-stage cancer, with patients seriously disturbed by fatigue, sleep disorders, bone pain, constipation and other disease related symptoms. As treatment and prognosis continues to improve, reducing symptoms and improving quality of life with minimum of toxicities have become important therapeutic goals. The effectiveness of abiraterone acetate and enzalutamide in both prolonging life and improving quality of life in asymptomatic or mildly symptomatic patients with metastatic castrations-resistant prostate cancer (mCRPC) has been clinically proven...
May 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28614061/a-genetic-variant-in-slc28a3-rs56350726-is-associated-with-progression-to-castration-resistant-prostate-cancer-in-a-korean-population-with-metastatic-prostate-cancer
#10
Jung Ku Jo, Jong Jin Oh, Yong Tae Kim, Hong Sang Moon, Hong Yong Choi, Seunghyun Park, Jin-Nyoung Ho, Sungroh Yoon, Hae Young Park, Seok-Soo Byun
BACKGROUND: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variants in mPCa and progression to CRPC. RESULTS: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612561/-prognostic-significance-of-erg-gene-rearrangement-and-protein-expression-in-prostate-cancer
#11
Xiu-Yi Pan, Jun-Ya Tan, Ling Nie, Xiao-Xue Yin, Jing Gong, Xue-Qin Chen, Qiao Zhou, Hao Zeng, Ni Chen
OBJECTIVES: To investigate gene rearrangement and protein expression of ETS related gene (ERG ) in prostate cancer of Chinese patients and its correlation with clinicopathological characteristics and prognosis. METHODS: This study collected 482 cases of prostatic adenocarcinomas diagnosed by prostate biopsy in West China Hospital of Sichuan University from 2009 to 2014. Fluorescencein situ hybridization (FISH) and immuno-histochemical staining (IHC) were performed to access the ERG rearrangement and protein expression respectively...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28609769/prediction-of-time-to-castration-resistant-prostate-cancer-using-bone-scan-index-in-men-with-metastatic-hormone-sensitive-prostate-cancer
#12
Yasuhide Miyoshi, Shuko Yoneyama, Takashi Kawahara, Yusuke Hattori, Jun-Ichi Teranishi, Jun-Ichi Ohta, Shigeo Takebayashi, Yumiko Yokomizo, Narihiko Hayashi, Hiroji Uemura
INTRODUCTION: We evaluated bone scan index (BSI) as a predictive biomarker for time to castration-resistant prostate cancer (CRPC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: We identified 85 consecutive mHSPC patients treated with first-line androgen deprivation therapy. We analyzed the correlations between time to CRPC and clinicopathological characteristics, including age, prostate-specific antigen (PSA) level, Gleason score, clinical TNM stage, hemoglobin, lactate dehydrogenase, C-reactive protein, and BSI...
June 14, 2017: Urologia Internationalis
https://www.readbyqxmd.com/read/28609657/ack1-tnk2-regulates-histone-h4-tyr88-phosphorylation-and-ar-gene-expression-in-castration-resistant-prostate-cancer
#13
Kiran Mahajan, Pavani Malla, Harshani R Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J Lawrence, Nupam P Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28606735/neutrophil-to-lymphocyte-ratio-in-castration-resistant-prostate-cancer-patients-treated-with-daily-oral-corticosteroids
#14
Niven Mehra, Adam Sharp, David Lorente, David Dolling, Semini Sumanasuriya, Bernadette Johnson, David Dearnaley, Chris Parker, Johann de Bono
BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to be highly prognostic across many tumor types, and predictive of treatment outcome in advanced prostate cancer, and has been postulated to be an indirect measure of tumor inflammation. We evaluated the effect of low-dose steroids on NLR in men suffering from castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: The NLR was evaluated in a prospective randomized phase II trial that compared prednisolone 5 mg twice daily and dexamethasone 0...
May 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#15
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28600675/a-novel-capillary-nano-immunoassay-for-assessing-androgen-receptor-splice-variant-7-in-plasma-correlation-with-cd133-antigen-expression-in-circulating-tumor-cells-a-pilot-study-in-prostate-cancer-patients
#16
J L García, R Lozano, I Misiewicz-Krzeminska, J Fernández-Mateos, P Krzeminski, S Alfonso, R A Marcos, R García, F Gómez-Veiga, Á Virseda, M Herrero, D Olmos, J J Cruz-Hernández
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform...
June 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28600580/outcomes-of-dose-attenuated-docetaxel-in-asian-patients-with-castrate-resistant-prostate-cancer
#17
Jia Wei Ang, Min-Han Tan, Miah Hiang Tay, Chee Keong Toh, Quan Sing Ng, Ravindran Kanesvaran
INTRODUCTION: High levels of toxicities have been observed when docetaxel is administered at the standard dose of 75 mg/m(2) every 3 weeks (Q3W) in the real-world treatment of Asian patients with metastatic castrate-resistant prostate cancer (CRPC). This study aimed to evaluate the efficacy and tolerability of 2 attenuated regimens more widely used in an Asian setting to minimise toxicity - 60 mg/m(2) Q3W and weekly docetaxel (20 mg/m(2) to 35 mg/m(2)). MATERIALS AND METHODS: Medical records of 89 CRPC patients between December 2003 and April 2013 were reviewed...
May 2017: Annals of the Academy of Medicine, Singapore
https://www.readbyqxmd.com/read/28592703/real-time-transferrin-based-pet%C3%A2-detects-myc-positive-prostate-cancer
#18
Rahul Aggarwal, Spencer Behr, Pamela L Paris, Charles Truillet, Matthew F L Parker, Loc T Huynh, Junnian Wei, Byron Hann, Jack Youngren, Gayatri Premasekharan, Jiaoti Huang, Nimna Ranatunga, Emily Chang, Kenneth T Gao, Charles J Ryan, Eric J Small, Michael J Evans
Non-invasive biomarkers that detect the activity of important oncogenic drivers could significantly improve cancer diagnosis and management of treatment. The goal of this study was to determine if 68Ga-citrate (which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor is a direct MYC target gene. Positron emission tomography (PET) imaging paired with 68Ga-citrate and molecular analysis of preclinical models, human cell-free DNA (cfDNA) and clinical biopsies were conducted to determine whether 68Ga-citrate can detect MYC-positive prostate cancer...
June 7, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28591577/androgen-receptor-deregulation-drives-bromodomain-mediated-chromatin-alterations-in-prostate-cancer
#19
Alfonso Urbanucci, Stefan J Barfeld, Ville Kytölä, Harri M Itkonen, Ilsa M Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R Jeffrey Karnes, Ashley E Ross, Edward M Schaeffer, Donald J Vander Griend, Stefan Knapp, Eva Corey, Felix Y Feng, Peter S Nelson, Fahri Saatcioglu, Karen E Knudsen, Teuvo L J Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G Mills
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28589901/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#20
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
May 19, 2017: Oncotarget
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