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https://www.readbyqxmd.com/read/28107193/microrna-744-promotes-prostate-cancer-progression-through-aberrantly-activating-wnt-%C3%AE-catenin-signaling
#1
Han Guan, Chunhui Liu, Fang Fang, Yeqing Huang, Tao Tao, Zhixin Ling, Zonghao You, Xu Han, Shuqiu Chen, Bin Xu, Ming Chen
Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#2
Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao
PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay...
January 19, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#3
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#4
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
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
#5
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/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#6
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/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/28062857/positive-feedback-loop-mediated-by-protein-phosphatase-1%C3%AE-mobilization-of-p-tefb-and-basal-cdk1-drives-androgen-receptor-in-prostate-cancer
#8
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/28055971/src-promotes-castration-recurrent-prostate-cancer-through-androgen-receptor-dependent-canonical-and-non-canonical-transcriptional-signatures
#9
Indranil Chattopadhyay, Jianmin Wang, Maochun Qin, Lingqiu Gao, Renae Holtz, Robert L Vessella, Robert W Leach, Irwin H Gelman
Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28042138/the-efficacy-and-safety-of-docetaxel-based-chemotherapy-combined-with-dexamethasone-1-mg-daily-oral-administration-jmto-pca-10-01-phase-ii-trial
#10
Nobumichi Tanaka, Kazuo Nishimura, Eijiro Okajima, Kenji Ina, Osamu Ogawa, Hirohiko Nagata, Koichiro Akakura, Kiyohide Fujimoto, Momokazu Gotoh, Satoshi Teramukai, Yoshihiko Hirao
OBJECTIVES: Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. MATERIALS AND METHODS: This study was a single-arm multi-institutional phase II trial...
January 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28041912/a-constitutive-intrinsic-inflammatory-signaling-circuit-composed-of-mir-196b-meis2-ppp3cc-and-p65-drives-prostate-cancer-castration-resistance
#11
Ji-Hak Jeong, Sun-Jin Park, Shohreh Iravani Dickinson, Jun-Li Luo
Androgen deprivation therapy is the most effective treatment for advanced prostate cancer, but almost all cancer eventually becomes castration resistant, and the underlying mechanisms are largely unknown. Here, we show that an intrinsic constitutively activated feedforward signaling circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC is formed during the emergence of castration-resistant prostate cancer (CRPC). This circuit controls the expression of stem cell transcription factors that drives the high tumorigenicity of CRPC cells...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28036278/a-novel-nonsense-mutation-in-androgen-receptor-confers-resistance-to-cyp17-inhibitor-treatment-in-prostate-cancer
#12
Dong Han, Shuai Gao, Kevin Valencia, Jude Owiredu, Wanting Han, Eric de Waal, Jill A Macoska, Changmeng Cai
The standard treatment for prostate cancer (PCa) is androgen deprivation therapy (ADT) that blocks transcriptional activity of androgen receptor (AR). However, ADT invariably leads to the development of castration-resistant PCa (CRPC) with restored activity of AR. CRPC can be further treated with CYP17 inhibitors to block androgen synthesis pathways, but most patients still relapse after a year of such treatment. The mechanisms that drive this progression are not fully understood, but AR activity, at least in a subset of cancers, appears to be restored again...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28026865/factors-predicting-skeletal-related-events-in-patients-with-bone-metastatic-castration-resistant-prostate-cancer
#13
Zachary Klaassen, Lauren E Howard, Amanda de Hoedt, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Stephen J Freedland
BACKGROUND: Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record. METHODS: Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013...
December 27, 2016: Cancer
https://www.readbyqxmd.com/read/28024400/cheminformatics-modeling-of-adverse-drug-responses-by-clinically-relevant-mutants-of-human-androgen-receptor
#14
Naman Paul, Lavinia A Carabet, Nada Lallous, Takeshi Yamazaki, Martin E Gleave, Paul S Rennie, Artem Cherkasov
The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug resistance develops in patients over time since they all target the mutation-prone androgen binding site (ABS), where gain-of-function mutations eventually convert antagonists into agonists. With a significant number of reported distinct mutations located across the ABS, it is imperative to develop a prognostic platform which would equip clinicians with prior knowledge and actionable strategies if cases of previously unreported AR mutations are encountered...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28011482/galectin-3-is-implicated-in-tumor-progression-and-resistance-to-anti-androgen-drug-through-regulation-of-androgen-receptor-signaling-in-prostate-cancer
#15
Tsogt-Ochir Dondoo, Tomoharu Fukumori, Kei Daizumoto, Tomoya Fukawa, Miho Kohzuki, Minoru Kowada, Yoshito Kusuhara, Hidehisa Mori, Hiroyoshi Nakatsuji, Masayuki Takahashi, Hiro-Omi Kanayama
BACKGROUND: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. MATERIALS AND METHODS: We examined tumor cell invasion and migration using the xCELLigence system...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28008150/prkar2b-plays-an-oncogenic-role-in-the-castration-resistant-prostate-cancer
#16
Jianjun Sha, Wei Xue, Baijun Dong, Jiahua Pan, Xiaorong Wu, Dong Li, Dongming Liu, Yiran Huang
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer. Despite some progresses have been made, the mechanism of CRPC development is still largely unknown, including the genes involved in its development have not been well defined. Here, we identifiedPRKAR2B to be a gene over-expressingin castration-resistant prostate cancer by analyzing the different online databases. Followed functional validation experiments showed that PRKAR2B promoted CRPC cell proliferation and invasion, and inhibited CRPC cell apoptosis...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000853/matrine-suppresses-invasion-of-castration-resistant-prostate-cancer-cells-by-downregulating-mmp-2-9-via-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Hai Huang, Tao Du, Guibin Xu, Yiming Lai, Xinxing Fan, Xianju Chen, Wenjiao Li, Fei Yue, Qi Li, Leyuan Liu, Kaiwen Li
Matrine is an alkaloid from Sophora flavescens that exhibits multiple protective effects on cancers. However, the molecular mechanisms of anti-metastatic effects of matrine on castration-resistant prostate cancer (CRPC) remain unknown. This study investigated the anti-metastatic effects of matrine on CRPC to identify the underlying mechanisms. The effects of matrine on the cell viability of DU145 and PC-3 cells were measured using MTS assay. The impact of matrine on expression levels of matrix metalloproteinase (MMP)-9, MMP-2, nuclear factor-κB (NF-κB) subunit p65 and phosphorylated p65 in cells untreated or treated with matrine were analyzed by western blotting...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27997745/impact-of-treatment-on-progression-to-castration-resistance-metastases-and-death-in-men-with-localized-high-grade-prostate-cancer
#18
Eric T Miller, Karim Chamie, Lorna Kwan, Michael S Lewis, Beatrice S Knudsen, Isla P Garraway
Men with high-grade prostate cancer (HGPC) are at greatest risk of disease progression. Clinical risk factors associated with castration-resistant prostate cancer (CRPC), metastases, and prostate cancer-specific mortality (PCSM) were identified in a contemporary HGPC cohort. Clinical data was collected from men diagnosed with Gleason sum (GS) ≥8 at the Greater Los Angeles Veterans Affairs (GLA-VA) Healthcare System between 2000 and 2013. Multivariable competing risks regression analyses assessed progression to CRPC, metastases, and PCSM within three treatment strata...
December 20, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27995113/feasibility-of-classical-secondary-hormonal-therapies-prior-to-docetaxel-therapy-in-japanese-patients-with-castration-resistant-prostate-cancer-multicenter-retrospective-study
#19
Shuya Kandori, Takayuki Yoshino, Masakazu Tsutsumi, Atsushi Yamauchi, Mikinobu Ohtani, Yoshiharu Fukuhara, Naoto Miyanaga, Jun Miyazaki, Hiroyuki Nishiyama, Toru Shimazui
BACKGROUND: We retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy. METHODS: The cases of 73 CRPC patients who underwent docetaxel therapy in 2005-2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate...
December 2016: Prostate International
https://www.readbyqxmd.com/read/27993795/gene-polymorphisms-in-antioxidant-enzymes-correlate-with-the-efficacy-of-androgen-deprivation-therapy-for-prostate-cancer-with-implications-of-oxidative-stress
#20
M Shiota, N Fujimoto, M Itsumi, A Takeuchi, J Inokuchi, K Tatsugami, A Yokomizo, S Kajioka, T Uchiumi, M Eto
BACKGROUND: Oxidative stress mitigated by antioxidant enzymes is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). This study investigated the association between genetic variations in antioxidant enzymes and the efficacy of ADT as well as its biological background. PATIENTS AND METHODS: The non-synonymous or promoter-locating polymorphisms of antioxidant enzymes were examined as well as the time to CRPC progression and overall survival in 104 and 92 patients treated with ADT for metastatic and non-metastatic prostate cancer, respectively...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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