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https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#1
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-inneuroendocrine-prostate-cancer
#2
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon M Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul K Azad, Xuhong Cao, Jeri Kim, Paul Corn, Christopher Logothetis, Ana M Aparicio, Arul M Chinnayan, Nora M Navone, Patricia Troncoso, Timothy C Thompson
PURPOSE: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphological criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for NEPC. RESULTS: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public datasets and a panel of 28 PDX models we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29132337/gene-expression-signatures-of-neuroendocrine-prostate-cancer-and-primary-small-cell-prostatic-carcinoma
#3
Harrison K Tsai, Jonathan Lehrer, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Tamara L Lotan
BACKGROUND: Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29063171/-neuroendocrine-prostate-cancer
#4
S Tritschler, R Erdelkamp, C Stief, M Hentrich
Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t‑NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase...
November 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28978002/establishment-of-a-neuroendocrine-prostate-cancer-model-driven-by-the-rna-splicing-factor-srrm4
#5
Yinan Li, Ruiqi Chen, Mary Bowden, Fan Mo, Yen-Yi Lin, Martin Gleave, Colin Collins, Xuesen Dong
Neuroendocrine prostate cancer (NEPC) is becoming more prevalent as more potent androgen receptor (AR) pathway inhibitors are applied to patients with metastatic tumors. However, there are limited cell and xenograft models currently available, hindering the investigation of signal pathways involved in regulating NEPC progression and the design of high throughput screening assays for inhibitors to treat NEPC patients. Here, we report an NEPC model, LnNE, that is derived from prostate adenocarcinoma cells and has global similarity in transcription and RNA splicing to tumors from NEPC patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28790115/msh2-loss-in-primary-prostate-cancer
#6
Liana B Guedes, Emmanuel S Antonarakis, Michael T Schweizer, Nooshin Mirkheshti, Fawaz Almutairi, Jong Chul Park, Stephanie Glavaris, Jessica Hicks, Mario A Eisenberger, Angelo M De Marzo, Jonathan I Epstein, William B Isaacs, James R Eshleman, Colin C Pritchard, Tamara L Lotan
Purpose: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary prostate tumors with MMR defects.Experimental Design: A total of 1,133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed by PCR and NGS (mSINGS).Results: Of primary adenocarcinomas and NEPC, 1...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28753573/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#7
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28727698/high-prevalence-of-neuropathic-pain-component-in-patients-with-low-back-pain-evidence-from-meta-analysis
#8
Kapil Gudala, Dipika Bansal, Rambabu Vatte, Babita Ghai, Fabrizio Schifano, Chandrasehkar Boya
BACKGROUND: Low back pain (LBP) is a complex syndrome which includes a nociceptive (NcP) component, a neuropathic (NeP) component, or a mixture of components (mixed pain). The NeP component (NePC) in LBP is defined as the presence of NeP with or without an NcP. OBJECTIVE: This meta-analysis aimed at assessing the pooled prevalence of NePC in patients with LBP and at identifying the factors causing significant heterogeneity in reported prevalence. STUDY DESIGN: Meta-analysis...
July 2017: Pain Physician
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
#9
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/28506524/contemporary-incidence-and-cancer-control-outcomes-of-primary-neuroendocrine-prostate-cancer-a-seer-database-analysis
#10
Emanuele Zaffuto, Raisa Pompe, Marc Zanaty, Helen Davis Bondarenko, Sami-Ramzi Leyh-Bannurah, Marco Moschini, Paolo Dell'Oglio, Giorgio Gandaglia, Nicola Fossati, Armando Stabile, Kevin C Zorn, Francesco Montorsi, Alberto Briganti, Pierre I Karakiewicz
INTRODUCTION: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity. We aimed at providing contemporary data on incidence and survival figures of de-novo NEPC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, we identified 309 individuals with de-novo NEPC diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over the study. Kaplan-Meier analyses assessed overall survival (OS) after stratification according to histologic subtype, metastatic status, and treatment...
April 13, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28482433/-clinical-characteristics-of-13-neuroendocrine-prostate-cancer-patients
#11
W H Zhang, T G Si, X L Yang, B Yang, C F Liu, H P Yu, W G Xing, Z Guo
Objective: To explore the radiological, pathological features and clinical characteristics of neuroendocrine prostate cancer patients(NEPC). Methods: The clinical characteristics and pathology data of 13 neuroendocrine prostate cancer patients treated in the Affiliated Hospital of Tianjin Medical University from January 2004 to January 2015 were analyzed retrospectively. Results: Of all 13 patients, three cases were primally diagnosed small cell cancer, and 10 cases were translated to neuroendocrine type from adenocarcinoma after endocrine therapy...
May 9, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#12
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28361223/emerging-variants-of-castration-resistant-prostate-cancer
#13
REVIEW
Panagiotis J Vlachostergios, Loredana Puca, Himisha Beltran
Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#14
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#15
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...
July 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28119771/usefulness-of-four-commonly-used-neuropathic-pain-screening-questionnaires-in-patients-with-chronic-low-back-pain-a-cross-sectional-study
#16
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
https://www.readbyqxmd.com/read/27784708/the-master-neural-transcription-factor-brn2-is-an-androgen-receptor-suppressed-driver-of-neuroendocrine-differentiation-in-prostate-cancer
#17
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
https://www.readbyqxmd.com/read/27772015/the-narrative-emotion-process-coding-system-2-0-a-multi-methodological-approach-to-identifying-and-assessing-narrative-emotion-process-markers-in-psychotherapy
#18
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
https://www.readbyqxmd.com/read/27728805/n-myc-induces-an-ezh2-mediated-transcriptional-program-driving-neuroendocrine-prostate-cancer
#19
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 cancer (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
https://www.readbyqxmd.com/read/27245506/prostate-cancer-srrm4-drives-nepc-progression
#20
Rebecca Kelsey
No abstract text is available yet for this article.
July 2016: Nature Reviews. Urology
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