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J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
Kapil Gudala, Babita Ghai, Dipika Bansal
BACKGROUND: Recently symptoms-based screening questionnaires have gained attention for screening for a neuropathic pain component (NePC) in various chronic pain conditions. The present study assessed the usefulness of four commonly used NePC screening questionnaires including the Self-completed douleur neuropathique 4 (S-DN4), the ID Pain, the painDETECT questionnaire (PDQ), and the Self-completed Leeds Assessment of neuropathic Symptoms and Signs (S-LANSS) questionnaire in patients with chronic low back pain (CLBP) to assess the presence of NePC...
January 2017: Korean Journal of Pain
Jennifer L Bishop, Daksh Thaper, Sepideh Vahid, Alastair Davies, Kirsi Ketola, Hidetoshi Kuruma, Randy Jama, Ka Mun Nip, Arkhjamil Angeles, Fraser Johnson, Alexander W Wyatt, Ladan Fazli, Martin E Gleave, Dong Lin, Mark A Rubin, Colin C Collins, Yuzhuo Wang, Himisha Beltran, Amina Zoubeidi
Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor-resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo Mechanistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2...
January 2017: Cancer Discovery
Lynne E Angus, Tali Boritz, Emily Bryntwick, Naomi Carpenter, Christianne Macaulay, Jasmine Khattra
OBJECTIVE: Recent studies suggest that it is not simply the expression of emotion or emotional arousal in session that is important, but rather it is the reflective processing of emergent, adaptive emotions, arising in the context of personal storytelling and/or Emotion-Focused Therapy (EFT) interventions, that is associated with change. METHOD: To enhance narrative-emotion integration specifically in EFT, Angus and Greenberg originally identified a set of eight clinically derived narrative-emotion integration markers were originally identified for the implementation of process-guiding therapeutic responses...
October 24, 2016: Psychotherapy Research: Journal of the Society for Psychotherapy Research
Etienne Dardenne, Himisha Beltran, Matteo Benelli, Kaitlyn Gayvert, Adeline Berger, Loredana Puca, Joanna Cyrta, Andrea Sboner, Zohal Noorzad, Theresa MacDonald, Cynthia Cheung, Ka Shing Yuen, Dong Gao, Yu Chen, Martin Eilers, Juan-Miguel Mosquera, Brian D Robinson, Olivier Elemento, Mark A Rubin, Francesca Demichelis, David S Rickman
The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancerĀ (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC...
October 10, 2016: Cancer Cell
Rebecca Kelsey
No abstract text is available yet for this article.
July 2016: Nature Reviews. Urology
Feng Sun, Zhi Wei Zhang, Ee Min Tan, Z L Ryan Lim, Yu Li, Xiao Chong Wang, Seok Eng Chua, Jun Li, Edwin Cheung, Eu-Leong Yong
Neuroendocrine prostate cancer (NEPC) has a poor prognosis, with a median survival of less than 1 year after diagnosis. Following androgen deprivation therapy, prostate adenocarcinoma cells have been observed to develop an androgen receptor-negative, terminally differentiated and indolent neuroendocrine-like phenotype. However, several molecular events, including interleukin 6 (IL-6) stimulation, in the prostate microenvironment result in the appearance of aggressive, highly proliferative castrate-resistant NEPC...
July 2016: Carcinogenesis
Meixiang Sang, Mohit Hulsurkar, Xiaochong Zhang, Haiping Song, Dayong Zheng, Yan Zhang, Min Li, Jianming Xu, Songlin Zhang, Michael Ittmann, Wenliang Li
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that commonly arises through neuroendocrine differentiation (NED) of prostate adenocarcinoma (PAC) after therapy, such as radiation therapy and androgen deprivation treatment (ADT). No effective therapeutic is available for NEPC and its molecular mechanisms remain poorly understood. We have reported that G protein-coupled receptor kinase 3 (GRK3, also called ADRBK2) promotes prostate cancer progression. In this study, we demonstrate that the ADT-activated cAMP response element binding protein (CREB) directly targets and induces GRK3...
July 19, 2016: Oncotarget
Yinan Li, Nilgun Donmez, Cenk Sahinalp, Ning Xie, Yuwei Wang, Hui Xue, Fan Mo, Himisha Beltran, Martin Gleave, Yuzhuo Wang, Colin Collins, Xuesen Dong
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer that typically does not respond to androgen receptor pathway inhibition (ARPI), and its diagnosis is increasing. OBJECTIVE: To understand how NEPC develops and to identify driver genes to inform therapy for NEPC prevention. DESIGN, SETTING, AND PARTICIPANTS: Whole-transcriptome sequencing data were extracted from prostate tumors from two independent cohorts: The Beltran cohort contained 27 adenocarcinoma and five NEPC patient samples, and the Vancouver Prostate Centre cohort contained three patient samples and nine patient-derived xenografts...
January 2017: European Urology
Kamlesh K Yadav, Khader Shameer, Ben Readhead, Shalini S Yadav, Li Li, Andrew Kasarskis, Ashutosh K Tewari, Joel T Dudley
BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men. More than 200,000 new cases are added each year in the US, translating to a lifetime risk of 1 in 7 men. Neuroendocrine prostate cancer (NEPC) is an aggressive and treatmentresistant form of prostate cancer. A subset of patients treated with aggressive androgen deprivation therapy (ADT) present with NEPC. Patients with NEPC have a reduced 5-year overall survival rate of 12.6%. Knowledge integration from genetic, epigenetic, biochemical and therapeutic studies suggests NEPC as an indicative mechanism of resistance development to various forms of therapy...
2016: Current Pharmaceutical Design
H Choe, A Sboner, H Beltran, D Nanus, S T Tagawa
INTRODUCTION: Neuroendocrine prostate cancer (NEPC) is an aggressive late-stage variant of PC that is often androgen-receptor negative. Most clinicians believe the VTE rate with NEPC is higher than with standard metastatic castration-resistant PC (mCRPC), but NEPC tends to present with bulkier visceral disease and include platinum chemotherapy unlike standard PC. In many solid tumors, a more aggressive phenotype correlates with increased VTE risk and elevated expression of coagulation factors...
April 2016: Thrombosis Research
Robert W Moore, Wayne A Fritz, Andrew J Schneider, Tien-Min Lin, Amanda M Branam, Stephen Safe, Richard E Peterson
It is well established that the prototypical aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can both cause and protect against carcinogenesis in non-transgenic rodents. But because these animals almost never develop prostate cancer with old age or after carcinogen exposure, whether AHR activation can affect cancer of the prostate remained unknown. We used animals designed to develop this disease, Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, to investigate the potential role of AHR signaling in prostate cancer development...
August 15, 2016: Toxicology and Applied Pharmacology
Francesco Crea, Erik Venalainen, Xinpei Ci, Hongwei Cheng, Larissa Pikor, Abhijit Parolia, Hui Xue, Nur Ridzwan Nur Saidy, Dong Lin, Wan Lam, Colin Collins, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm. NEPC is thought to originate from the transdifferentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/noncoding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drug-resistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, miRNAs) play a key role in NEPC initiation and progression...
May 2016: Epigenomics
Tali Boritz, Ryan Barnhart, Lynne Angus, Michael J Constantino
OBJECTIVE: This study aimed to further understand how narrative flexibility contributes to therapeutic outcome in brief psychotherapy for depression utilizing the Narrative-Emotion Process Coding System (NEPCS), an observational measure that identifies specific markers of narrative and emotion integration in therapy sessions. METHOD: The present study investigated narrative flexibility by examining the contribution of NEPCS shifting (i.e., movement between NEPCS markers) in early, middle, and late sessions of client-centred therapy (CCT), emotion-focused therapy (EFT), and cognitive therapy (CT) and treatment outcome (recovered versus unchanged at the therapy termination)...
April 19, 2016: Psychotherapy Research: Journal of the Society for Psychotherapy Research
(no author information available yet)
Overexpression of MYCN in normal basal prostate cells drives formation of metastatic NEPC.
June 2016: Cancer Discovery
John K Lee, John W Phillips, Bryan A Smith, Jung Wook Park, Tanya Stoyanova, Erin F McCaffrey, Robert Baertsch, Artem Sokolov, Justin G Meyerowitz, Colleen Mathis, Donghui Cheng, Joshua M Stuart, Kevan M Shokat, W Clay Gustafson, Jiaoti Huang, Owen N Witte
MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone...
April 11, 2016: Cancer Cell
Himisha Beltran, Adam Jendrisak, Mark Landers, Juan Miguel Mosquera, Myriam Kossai, Jessica Louw, Rachel Krupa, Ryon P Graf, Nicole A Schreiber, David M Nanus, Scott T Tagawa, Dena Marrinucci, Ryan Dittamore, Howard I Scher
PURPOSE: The transition of prostate adenocarcinoma to a predominantly androgen receptor (AR) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression +/- the development of small-cell or neuroendocrine tumor characteristics. As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning toward a neuroendocrine phenotype (NEPC). EXPERIMENTAL DESIGN: We prospectively studied a metastatic tumor biopsy, serum biomarkers, and circulating tumor cells (CTC, Epic Sciences) from patients with castration-resistant prostate cancer (CRPC) including those with pure or mixed NEPC histology present on biopsy...
March 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Murali Gururajan, Karen A Cavassani, Margarit Sievert, Peng Duan, Jake Lichterman, Jen-Ming Huang, Bethany Smith, Sungyong You, Srinivas Nandana, Gina Chia-Yi Chu, Sheldon Mink, Sajni Josson, Chunyan Liu, Matteo Morello, Lawrence W M Jones, Jayoung Kim, Michael R Freeman, Neil Bhowmick, Haiyen E Zhau, Leland W K Chung, Edwin M Posadas
FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF...
December 29, 2015: Oncotarget
A Kretschmer, C Wittekind, C G Stief, C Gratzke
BACKGROUND: Neuroendocrine carcinoma of the prostate (NEPC) is a rare, androgen-independent variant of prostate cancer with increasing incidence of over the past few years. It commonly progresses rapidly and is associated with a poor prognosis. Based on a different tumor biology compared to adenocarcinomas of the prostate, standard therapeutic approaches for prostate cancer are ineffective. To date, no specific treatment for NEPC exists. OBJECTIVES: The purpose of this work is to provide an overview of current histopathologic characteristics, histomorphologic classifications, and current as well as future treatment options for NEPC...
December 2015: Der Urologe. Ausg. A
Kunal C Kadakia, Scott A Tomlins, Saagar K Sanghvi, Andi K Cani, Kei Omata, Daniel H Hovelson, Chia-Jen Liu, Kathleen A Cooney
IMPORTANCE: Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting. OBJECTIVE: To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. DESIGN, SETTING, AND PARTICIPANTS: A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9)...
October 6, 2015: Journal of Hematology & Oncology
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