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https://www.readbyqxmd.com/read/28334734/multinucleated-polyploidy-drives-resistance-to-docetaxel-chemotherapy-in-prostate-cancer
#1
Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28327891/somatic-brca2-bi-allelic-loss-in-the-primary-prostate-cancer-was-associated-to-objective-response-to-parpi-in-a-sporadic-crpc-patient
#2
N Romero-Laorden, E Piñeiro-Yañez, A Gutierrez-Pecharoman, M I Pacheco, E Calvo, F Al-Shahrour, E Castro, D Olmos
No abstract text is available yet for this article.
February 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#3
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#4
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28302580/the-role-of-therapeutic-layering-in-optimizing-treatment-for-patients-with-castration-resistant-prostate-cancer-radar-ii
#5
E David Crawford, Daniel P Petrylak, Neal Shore, Fred Saad, Susan F Slovin, Nicholas J Vogelzang, Thomas E Keane, Phillip J Koo, Leonard G Gomella, Joe M O'Sullivan, Bertrand Tombal, Raoul S Concepcion, Paul Sieber, Nelson N Stone, Steven E Finkelstein, Evan Y Yu
OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific CRPC treatments. MATERIALS AND METHODS: The RADAR II [Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence] Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for mCRPC based on available data and clinical experience...
March 13, 2017: Urology
https://www.readbyqxmd.com/read/28295408/circulating-tumor-cells-as-a-marker-for-progression-free-survival-in-metastatic-castration-na%C3%A3-ve-prostate-cancer
#6
Andreas Josefsson, Anna Linder, Despina Flondell Site, Giacomo Canesin, Anna Stiehm, Aseem Anand, Anders Bjartell, Jan-Erik Damber, Karin Welén
BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study...
March 10, 2017: Prostate
https://www.readbyqxmd.com/read/28289967/a-pilot-trial-evaluating-zoledronic-acid-induced-changes-in-18-f-fmau-positron-emission-tomography-imaging-of-bone-metastases-in-prostate-cancer
#7
Ulka N Vaishampayan, Omid S Tehrani, Jawana M Lawhorn-Crews, Lance K Heilbrun, Kimberlee Dobson, Daryn Smith, Brenda Dickow, Anthony F Shields
PURPOSE: We conducted a pilot trial utilizing [(18)F]FMAU [1-(2'-deoxy-2'-[(18)F]fluoro-β-D-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM). PROCEDURES: Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min...
March 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28285412/symptoms-and-impacts-in-non-metastatic-castration-resistant-prostate-cancer-qualitative-study-findings
#8
Erin L Tomaszewski, Pierre Moise, Robert N Krupnick, Jared Downing, Margaret Meyer, Shevani Naidoo, Stefan Holmstrom
OBJECTIVES: We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). METHODS: A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC...
March 11, 2017: Patient
https://www.readbyqxmd.com/read/28283376/navigating-the-evolving-therapeutic-landscape-in-advanced-prostate-cancer
#9
REVIEW
E David Crawford, Daniel Petrylak, Oliver Sartor
Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year. The overall 5-year survival rate for prostate cancer is very high. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop castration-resistant prostate cancer (CRPC) within 5 years, with median survival for those with metastatic CRPC ranging from approximately 15 to 36 months in recent studies. With the advent of several new drugs in the past 5 years to treat CRPC, the challenge facing clinicians is how to best sequence or combine therapies or both to optimize outcomes...
March 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28282611/phase-ib-dose-finding-study-of-abiraterone-acetate-plus-buparlisib-bkm120-or-dactolisib-bez235-in-patients-with-castration-resistant-prostate-cancer
#10
Christophe Massard, Kim Nguyen Chi, Daniel Castellano, Johann de Bono, Gwenaelle Gravis, Luc Dirix, Jean-Pascal Machiels, Alain Mita, Begona Mellado Gonzalez, Sabine Turri, Joan Maier, Denes Csonka, Arunava Chakravartty, Karim Fizazi
BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28280729/silencing-capn2-expression-inhibited-castration-resistant-prostate-cancer-cells-proliferation-and-invasion-via-akt-mtor-signal-pathway
#11
Pu Li, Chenkui Miao, Chao Liang, Pengfei Shao, Zengjun Wang, Jie Li
The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3) than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2) and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28278515/phase-2-study-of-circulating-microrna-biomarkers-in-castration-resistant-prostate-cancer
#12
Hui-Ming Lin, Kate L Mahon, Calan Spielman, Howard Gurney, Girish Mallesara, Martin R Stockler, Patricia Bastick, Karen Briscoe, Gavin Marx, Alexander Swarbrick, Lisa G Horvath
BACKGROUND: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings. METHODS: Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients...
March 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28277852/the-treatment-patterns-of-castration-resistant-prostate-cancer-in-japan-including-symptomatic-skeletal-events-and-associated-treatment-and-healthcare-resource-use
#13
Hiroji Uemura, Marco DiBonaventura, Ed Wang, Dianne Athene Ledesma, Kristen Concialdi, Yasuko Aitoku
BACKGROUND: Real-world treatment patterns of bone metastatic castration-resistant prostate cancer (mCRPC) in Japan were examined, focusing on treatment patterns and resource use differences attributed to symptomatic skeletal events (SSEs). METHODS: Urologists (N=176) provided retrospective chart data for patients with mCRPC (N=445) via online surveys. Descriptive analyses and chi-square tests evaluated treatment patterns and their differences by SSE presence; generalized linear mixed models examined healthcare resource utilization differences as a function of SSEs...
March 6, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28275218/epigenomic-regulation-of-androgen-receptor-signaling-potential-role-in-prostate-cancer-therapy
#14
REVIEW
Vito Cucchiara, Joy C Yang, Vincenzo Mirone, Allen C Gao, Michael G Rosenfeld, Christopher P Evans
Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome...
January 16, 2017: Cancers
https://www.readbyqxmd.com/read/28264534/-low-dose-estramustine-phosphate-monotherapy-in-castration-resistant-prostate-cancer-patients
#15
Tomohiro Fukui, Kenji Nakamura, Toru Sakatani, Takeshi Atsuta, Takuma Kato, Tetsuya Fukumoto, Masaaki Ito, Koji Inoue, Akito Terai
We retrospectively evaluated the efficacy and toxicity of low-dose estramustine phosphate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC). We administered EMP at 140 or 280 mg/day to 89 patients between January 2003 and December 2012. None of the patients were receiving concomitant dexamethasone and none had ever been treated with docetaxel. Fifty-three patients (59.6%) experienced a decline in prostate-specific antigen (PSA) levels, including 20 (22.5%) with a decline of more than 50%...
February 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28264478/crosstalk-of-the-androgen-receptor-with-transcriptional-collaborators-potential-therapeutic-targets-for-castration-resistant-prostate-cancer
#16
REVIEW
Daisuke Obinata, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC)...
February 28, 2017: Cancers
https://www.readbyqxmd.com/read/28256535/rest-is-a-crucial-regulator-for-acquiring-emt-like-and-stemness-phenotypes-in-hormone-refractory-prostate-cancer
#17
Yi-Ting Chang, Tzu-Ping Lin, Mel Campbell, Chin-Chen Pan, Shu-Hui Lee, Hsin-Chen Lee, Muh-Hwa Yang, Hsing-Jien Kung, Pei-Ching Chang
Castration-resistance prostate cancer (CRPC), also known as hormone-refractory prostate cancer (HRPC), requires immediate attention since it is not only resistant to androgen ablation, chemo- and radiotherapy, but also highly metastatic. Increasing evidence suggests that enrichment of neuroendocrine (NE) cells is associated with CRPC. Here, combined RNA-seq and ChIP-seq analysis reveals that REST is involved in epithelial-mesenchymal transition (EMT) and stemness acquisition in NE differentiated prostate cancer (PCa) cells via direct transcriptional repression of Twist1 and CD44...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255661/ccn3-ezh2-ar-feedback-loop-new-targets-for-enzalutamide-and-castration-resistant-prostate-cancer
#18
Cameron M Armstrong, Allen C Gao
The development of castration resistant prostate cancer and anti-androgen resistance remains one of the largest hurdles in the successful treatment of prostate cancer. Therefore, the identification of dysregulated pathways contributing to this resistance and determining ways to target these mechanisms is of utmost importance. In the recent publication in Cancer Research, Fong et al. identify a novel role for cytoplasmic CCN3 in prostate cancer progression and enzalutamide resistance. The authors demonstrate that CCN3 expression inhibits androgen receptor signaling and thereby suppresses enzalutamide-resistant prostate cancer cell proliferation, colony formation, and xenograft tumor growth...
March 2, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28253524/intracrine-androgen-biosynthesis-in-renal-cell-carcinoma
#19
Geun Taek Lee, Christopher S Han, Young Suk Kwon, Rutveej Patel, Parth K Modi, Seok Joo Kwon, Izak Faiena, Neal Patel, Eric A Singer, Han-Jong Ahn, Wun-Jae Kim, Isaac Y Kim
BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells...
March 2, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28252832/inactivation-of-id4-promotes-a-crpc-phenotype-with-constitutive-ar-activation-through-fkbp52
#20
Jugal Bharat Joshi, Divya Patel, Derrick J Morton, Pankaj Sharma, Jin Zou, Dhanushka Hewa Bostanthirige, Yamini Gorantla, Peri Nagappan, Shravan Kumar Komaragiri, Jeffrey C Sivils, Huan Xie, Ravi Palaniappan, Guangdi Wang, Marc B Cox, Jaideep Chaudhary
Castration-resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen-depleted environment of the prostate. In recent years, targeting multiple chaperones and co-chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant-negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice...
November 27, 2016: Molecular Oncology
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