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https://www.readbyqxmd.com/read/27928807/prognostic-value-of-circulating-tumor-cells-in-castration-resistant-prostate-cancer-a-meta-analysis
#1
Yuxiao Zheng, Cheng Zhang, Jie Wu, Gong Cheng, Haiwei Yang, Lixin Hua, Zengjun Wang
PURPOSE: The prognostic value of circulating tumor cells (CTC) detected in castration-resistant prostate cancer(CRPC) is currently under debate. The aim of our meta-analysis was to evaluate the prognostic effect of CTC andto elucidate whether the detection of CTC in the peripheral blood (PB) of patients diagnosed with CRPC can beused as an independent prognostic factor for survival. MATERIALS AND METHODS: The Pubmed, Science Citation Index, Cochrane Database, Embase Cell Research databaseand the references in relevant studies were systematically searched...
December 8, 2016: Urology Journal
https://www.readbyqxmd.com/read/27924136/prognostic-value-of-inflammation-in-prostate-cancer-progression-and-response-to-therapeutic-a-critical-review
#2
REVIEW
Alessandro Sciarra, Alessandro Gentilucci, Stefano Salciccia, Federico Pierella, Flavio Del Bianco, Vincenzo Gentile, Ida Silvestri, Susanna Cattarino
Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a factor involved in prostate cancer (PC) pathogenesis and progression. This review critically analyzes the role of inflammation as a prognostic factor for progression and aggressiveness of PC. We verified the last 10 years literature data on the association between inflammation and PC aggressiveness, or PC response to therapies...
2016: Journal of Inflammation
https://www.readbyqxmd.com/read/27919973/bone-targeted-novel-cytotoxic-polybisphosphonate-conjugate-in-castration-resistant-prostate-cancer-a-multicenter-phase-1-study
#3
Camilla Thellenberg-Karlsson, Claes Nyman, Sten Nilsson, René Blom, Marcela Márquez, Enrique Castellanos, Anders R Holmberg
BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27916908/epidermal-growth-factor-receptor-status-in-circulating-tumor-cells-as-a-predictive-biomarker-of-sensitivity-in-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-chemotherapy
#4
Takatsugu Okegawa, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) can be used to predict survival in a population of bone-metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel chemotherapy. METHODS: All patients with mCRPC who had experienced treatment failure with androgen-deprivation therapy and had received docetaxel chemotherapy were eligible. CTCs and EGFR expression in CTCs were enumerated with the CellSearch System in whole blood...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916435/analytical-validation-of-androgen-receptor-splice-variant-7-detection-in-a-clinical-laboratory-improvement-amendments-clia-laboratory-setting
#5
Parvez M Lokhandwala, Stacy L Riel, Lisa Haley, Changxue Lu, Yan Chen, John Silberstein, Yezi Zhu, Gang Zheng, Ming-Tseh Lin, Christopher D Gocke, Alan W Partin, Emmanuel S Antonarakis, Jun Luo, James R Eshleman
Patients with castration-resistant prostate cancer (CRPC) often are treated with drugs that target the androgen receptor (AR) ligand-binding domain. Constitutively active AR splice variant 7 (AR-V7) lacks the ligand-binding domain and, if detected in circulating tumor cells, may be associated with resistance to these agents. We validated an AR-V7 assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Circulating tumor cells were isolated, and mRNA was reverse-transcribed into cDNA...
December 1, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27910803/the-prognostic-and-predictive-value-of-tmprss2-erg-gene-fusion-and-erg-protein-expression-in-prostate-cancer-biopsies
#6
Kasper Drimer Berg
BACKGROUND: The clinical course of prostate carcinoma (PCa) is very heterogeneous. Consequently, a personalised approach for risk stratification and treatment planning is important. Recently, it has become evident that PCa, also at the genomic level, is heterogeneous. An early and common alteration is the gene fusion between the transmembrane protease serine 2 (TMPRSS2) gene and the v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene resulting in expression of the oncoprotein ERG...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27897170/truncation-and-constitutive-activation-of-the-androgen-receptor-by-diverse-genomic-rearrangements-in-prostate-cancer
#7
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/27892725/investigational-serine-threonine-kinase-inhibitors-against-prostate-cancer-metastases
#8
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
#9
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
#10
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/27883295/identification-of-novel-snps-associated-with-risk-and-prognosis-in-patients-with-castration-resistant-prostate-cancer
#11
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/27869166/skp2-loss-destabilizes-ezh2-by-promoting-traf6-mediated-ubiquitination-to-suppress-prostate-cancer
#12
W Lu, S Liu, B Li, Y Xie, M G Izban, B R Ballard, S A Sathyanarayana, S E Adunyah, R J Matusik, Z Chen
EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27856956/the-efflux-transporter-abcg2-maintains-prostate-stem-cells
#13
Neha G Sabnis, Austin Miller, Mark A Titus, Wendy J Huss
: Prostate Stem Cells (PSCs) are characterized by their intrinsic resistance to Androgen Deprivation Therapy (ADT), possibly due to the lack of Androgen Receptor (AR) expression. PSCs resistance to ADT and PSC expansion in Castration Recurrent Prostate Cancer (CRPC) has sparked great interest in using differentiation therapy as an adjuvant to ADT. Understanding the mechanisms, by which PSCs maintain their undifferentiated phenotype, thus has important implications in differentiation therapy...
November 17, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27847272/3d-qsar-studies-of-3-3-4-dihydroisoquinolin-2-1h-ylsulfonyl-benzoic-acids-as-akr1c3-inhibitors-highlight-the-importance-of-molecular-docking-in-conformation-generation
#14
Xuehua Zheng, Yinuo Wu, Deyan Wu, Xinhua Wang, Chao Zhang, Xiaolei Guo, Hai-Bin Luo
AKR1C3 is a promising drug target for castration-resistant prostate cancer (CRPC). Here, 3D-QSAR analysis were performed on 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids to correlate their chemical structures with their observed AKR1C3 inhibitory activity. Three structural alignment methods employing various conformers were used to scrutinize the effect of conformation selection on the predictive accuracy of QSAR models. Using docked conformation, the best CoMFA and CoMSIA models were developed and validated with a training set of 61 molecules and a test set of 7 molecules...
November 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27843207/chemotherapy-options-in-castration-resistant-prostate-cancer
#15
REVIEW
Benjamin A Teply, Ralph J Hauke
INTRODUCTION: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. METHODS: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27837416/a-simple-prognostic-model-involving-prostate-specific-antigen-alkaline-phosphatase-and-albumin-for-predicting-the-time-required-to-progress-to-castration-resistant-prostate-cancer-in-patients-who-received-androgen-deprivation-therapy
#16
Wei Lv, Hongxiang Shang, Xinqi Pei, Yule Chen, Hongjun Xie, Dalin He, Xinyang Wang, Lei Li
PURPOSE: To distinguish potential biomarkers and build a useful model to predict the time required to progress to castration-resistant prostate cancer (CRPC) in patients with prostate cancer who have been treated with androgen deprivation therapy (ADT). METHODS: We considered 168 patients who received ADT as the initial therapy. Complete clinical data including age, tumor stage, Gleason score, prostate-specific antigen (PSA), complete blood count and liver function tests were analyzed...
November 11, 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27835608/pc-1-works-in-conjunction-with-e3-ligase-chip-to-regulate-androgen-receptor-stability-and-activity
#17
Jian Wang, Hui Zhang, Xiaoqing Zhang, Peng Wang, Hongtao Wang, Fang Huang, Chenyan Zhou, Jianguang Zhou, Shanhu Li
The androgen receptor (AR) is not only a ligand-dependent transcription factor, but also functions as a licensing factor, a component of DNA replication, which is degraded during mitosis. Furthermore, the deregulation of AR activity is involved in the initiation of prostate cancer and contributes to castration resistant prostate cancer (CRPC). While AR degradation is known to occur primarily through a proteasome-mediated pathway, very little is known about how this process is regulated, especially in M phase...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27830724/activation-of-ampk%C3%AE-mediates-additive-effects-of-solamargine-and-metformin-on-suppressing-muc1-expression-in-castration-resistant-prostate-cancer-cells
#18
SongTao Xiang, QiuHong Zhang, Qing Tang, Fang Zheng, JingJing Wu, LiJun Yang, Swei Sunny Hann
Prostate cancer is the second most common cause of cancer-related deaths worldwide. The mucin 1 (MUC1) oncoprotein is highly expressed in human prostate cancers with aggressive features. However, the role for MUC1 in occurrence and progression of castration-resistant prostate cancer (CRPC) remained elusive. In this study, we showed that solamargine, a major steroidal alkaloid glycoside, inhibited the growth of CRPC cells, which was enhanced in the presence of metformin. Furthermore, we found that solamargine increased phosphorylation of AMPKα, whereas reducing the protein expression and promoter activity of MUC1...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825118/amplification-of-muc1-in-prostate-cancer-metastasis-and-crpc-development
#19
Nicholas Wong, Pierre Major, Anil Kapoor, Fengxiang Wei, Judy Yan, Tariq Aziz, Mingxing Zheng, Dulitha Jayasekera, Jean-Claude Cutz, Mathilda Jing Chow, Damu Tang
Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27818287/clinical-significance-of-epithelial-mesenchymal-transition-emt-markers-in-prostate-cancer
#20
Sandy Figiel, Caroline Vasseur, Franck Bruyere, Francois Rozet, Karine Maheo, Gaelle Fromont
The process of epithelial-to-mesenchymal transition (EMT) contributes to cancer progression, with activation of transcription factors leading to loss of epithelial characteristics and acquirement of mesenchymal properties. We analyzed in human prostate cancer (PCa) the expression of EMT markers at the different stages of PCa natural history, and evaluated its clinical significance. The expression of the key EMT transcription factor Zeb1, together with E-cadherin, vimentin, and N-cadherin, was evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate (n=58), clinically localized cancer (CLC) (n=242), castration resistant PCa (CRPC) (n=48), and metastases (n=43)...
November 3, 2016: Human Pathology
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