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neuroendocrine prostate cancer

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https://www.readbyqxmd.com/read/29790189/the-identification-of-a-novel-antibody-for-cd133-using-human-antibody-phage-display
#1
Paige M Glumac, Colleen L Forster, Hong Zhou, Paari Murugan, Shilpa Gupta, Aaron M LeBeau
BACKGROUND: The transmembrane glycoprotein CD133 is believed to be a marker of adult prostate stem cells and cancer stem/initiating cells. Investigating the role of CD133 in the normal biology of the prostate and in cancer is complicated by the lack of a sensitive and accurate antibody for its detection. Here, we describe the characterization of a unique antibody identified using human antibody phage display that can recognize CD133 in both formalin-fixed tissues and cell lines. METHODS: A human single-chain variable fragment (scFv) antibody phage display library possessing a diversity of 8 × 109 was screened against fully glycosylated recombinant CD133...
May 22, 2018: Prostate
https://www.readbyqxmd.com/read/29760221/development-and-validation-of-a-prostate-cancer-genomic-signature-that-predicts-early-adt-treatment-response-following-radical-prostatectomy
#2
Mohammed Alshalalfa, R Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Bruce J Trock, Ashley E Ross, Kasra Yousefi, Harrison K Tsai, Shuang G Zhao, Jeffrey J Tosoian, Zaid Haddad, Mandeep Takhar, S Laura Chang, Daniel E Spratt, Firas Abdollah, Robert B Jenkins, Eric A Klein, Paul L Nguyen, Adam P Dicker, Robert B Den, Elai Davicioni, Felix Y Feng, Tamara L Lotan, Edward M Schaeffer
PURPOSE: Currently no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy (RP) for high risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT. EXPERIMENTAL DESIGN: A training set consisting of 284 RP patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT(a-ADT) treated and no-ADT treated groups...
May 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29759485/roles-of-alternative-rna-splicing-of-the-bif-1-gene-by-srrm4-during-the-development-of-treatment-induced-neuroendocrine-prostate-cancer
#3
Yu Gan, Yinan Li, Zhi Long, Ahn R Lee, Ning Xie, Jessica M Lovnicki, Yuxin Tang, Xiang Chen, Jiaoti Huang, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that becomes more prevalent when hormonal therapy, chemotherapy, or radiation therapy is applied to patients with metastatic prostate adenocarcinoma (AdPC). How AdPC cells survive these anti-cancer therapies and progress into t-NEPC remains unclear. By comparing the whole transcriptomes between AdPC and t-NEPC, we identified Bif-1, an apoptosis-associated gene, which undergoes alternative RNA splicing in t-NEPC...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#4
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29748904/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-alters-hyperpolarized-pyruvate-to-lactate-conversion-and-lactate-levels-in-vivo
#5
Niki Zacharias, Jaehyuk Lee, Sumankalai Ramachandran, Sriram Shanmugavelandy, James McHenry, Prasanta Dutta, Steven Millward, Seth Gammon, Eleni Efstathiou, Patricia Troncoso, Daniel E Frigo, David Piwnica-Worms, Christopher J Logothetis, Sankar N Maity, Mark A Titus, Pratip Bhattacharya
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors...
May 10, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#6
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29747035/microscale-radiosynthesis-preclinical-imaging-and-dosimetry-study-of-18-f-ambf-3-tate-a-potential-pet-tracer-for-clinical-imaging-of-somatostatin-receptors
#7
Ksenia Lisova, Maxim Sergeev, Susan Evans-Axelsson, Andreea D Stuparu, Seval Beykan, Jeffrey Collins, Jason Jones, Michael Lassmann, Ken Herrmann, David Perrin, Jason T Lee, Roger Slavik, R Michael van Dam
BACKGROUND: Peptides labeled with positron-emitting isotopes are emerging as a versatile class of compounds for the development of highly specific, targeted imaging agents for diagnostic imaging via positron-emission tomography (PET) and for precision medicine via theranostic applications. Despite the success of peptides labeled with gallium-68 (for imaging) or lutetium-177 (for therapy) in the clinical management of patients with neuroendocrine tumors or prostate cancer, there are significant advantages of using fluorine-18 for imaging...
April 20, 2018: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29736318/androgen-receptor-signaling-regulates-t-type-ca-2-channel-expression-and-neuroendocrine-differentiation-in-prostate-cancer-cells
#8
Megan Hall, Bryan Todd, Edwin D Allen, Nga Nguyen, Yoon-Jung Kwon, Vu Nguyen, Jennifer L Hearne, Miguel Martin-Caraballo
Therapies designed to reduce androgen production or receptor activation are effective in limiting prostate tumor growth. However, prolonged treatment with anti-androgen therapies results in the progression of prostate cancers into an androgen refractory state. Neuroendocrine differentiation (NED) has been associated with the progression of prostate cancers to an androgen resistant phenotype. In this work we investigated the effect of disrupting androgen receptor signaling in promoting NED of prostate carcinoma cells and whether it is accompanied by an increase in T-type Ca2+ channel expression...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29732998/an-overview-of-targeted-alpha-therapy-with-225actinium-and-213bismuth
#9
Alfred Morgenstern, Christos Apostolidis, Clemens Kratochwil, Mike Sathekge, Leszek Krolicki, Frank Bruchertseifer
Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA-617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer.
May 1, 2018: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29728311/expression-of-neuroendocrine-differentiation-markers-in-lethal-metastatic-castration-resistant-prostate-cancer
#10
Miika Sainio, Tapio Visakorpi, Teemu Tolonen, Joanna Ilvesaro, G Steven Bova
Neuroendocrine differentiation (NED) is a common phenomenon in prostate cancer, and it has been associated with poor prognosis in some studies of primary prostate cancer. Incidence and patterns of NED in metastatic prostate cancer sites have not been examined widely. In this study, we studied expression of three commonly used markers of NED (chromogranin A, neuron specific enolase and synaptophysin) in 89 metastases from 31 men that died of castration-resistant prostate cancer and underwent rapid autopsy, and in 89 hormone-naïve primary tumors removed by radical prostatectomy...
April 26, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29721191/microrna-652-induces-ned-in-lncap-and-emt-in-pc3-prostate-cancer-cells
#11
Robert K Nam, Tania Benatar, Yutaka Amemiya, Christopher J D Wallis, Joan Miguel Romero, Melina Tsagaris, Christopher Sherman, Linda Sugar, Arun Seth
MicroRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. Dysregulation of miRNAs is frequently associated with disease and, in particular, is involved in prostate cancer progression. Next generation miRNA sequencing identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. High expression of one of these five miRNAs, miR-652, correlated significantly with an increased rate of prostate cancer biochemical recurrence. Overexpression of miR-652 in prostate cancer cells, PC3 and LNCaP, resulted in increased growth, migration and invasion...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29707793/interleukin-6-induces-vegf-secretion-from-prostate-cancer-cells-in-a-manner-independent-of-androgen-receptor-activation
#12
Kenichiro Ishii, Takeshi Sasaki, Kazuhiro Iguchi, Shinya Kajiwara, Manabu Kato, Hideki Kanda, Yoshifumi Hirokawa, Kiminobu Arima, Atsushi Mizokami, Yoshiki Sugimura
BACKGROUND: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway...
April 29, 2018: Prostate
https://www.readbyqxmd.com/read/29696999/sexual-well-being-and-diurnal-cortisol-after-prostate-cancer-treatment
#13
Michael A Hoyt, Allison E Gaffey, Ashley W Wang, Mark S Litwin, Catalina J Lawsin
Sexual dysfunction and psychological distress are common after prostate cancer. Research has not examined the role of neuroendocrine markers of stress (e.g. cortisol). This study examines whether sexual functioning or sexual bother is associated with diurnal cortisol. Men treated for prostate cancer completed the University of California-Los Angeles Prostate Cancer Index and provided saliva samples four times daily for cortisol assessment. Higher sexual bother, but not sexual functioning, was associated with steeper cortisol slope...
April 1, 2018: Journal of Health Psychology
https://www.readbyqxmd.com/read/29686080/systemic-surfaceome-profiling-identifies-target-antigens-for-immune-based-therapy-in-subtypes-of-advanced-prostate-cancer
#14
John K Lee, Nathanael J Bangayan, Timothy Chai, Bryan A Smith, Tiffany E Pariva, Sangwon Yun, Ajay Vashisht, Qingfu Zhang, Jung Wook Park, Eva Corey, Jiaoti Huang, Thomas G Graeber, James Wohlschlegel, Owen N Witte
Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666783/development-of-neuroendocrine-prostate-cancers-by-the-ser-arg-repetitive-matrix-4-mediated-rna-splicing-network
#15
Ahn R Lee, Nicole Che, Jessica M Lovnicki, Xuesen Dong
While the use of next-generation androgen receptor pathway inhibition (ARPI) therapy has significantly increased the survival of patients with metastatic prostate adenocarcinoma (AdPC), several groups have reported a treatment-resistant mechanism, whereby cancer cells can become androgen receptor (AR) indifferent and gain a neuroendocrine (NE)-like phenotype. This subtype of castration-resistant prostate cancer has been termed "treatment-induced castration-resistant neuroendocrine prostate cancer" (CRPC-NE)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29659395/loss-of-psma-expression-in-non-neuroendocrine-dedifferentiated-acinar-prostate-cancer
#16
Peter Bronsert, Kathrin Reichel, Juri Ruf
The introduction of tracers targeting the prostate-specific membrane antigen (PSMA) has revolutionized PET imaging of acinar prostate adenocarcinoma. In general, an increasing PSMA expression is assumed with increasing dedifferentiation. Whereas loss of PSMA expression has been reported in case of neuroendocrine dedifferentiation, we present a patient with acinar prostate adenocarcinoma with a loss of PSMA expression after chemotherapy on PET/CT and in histological and immunohistochemical analyses. All tissue samples indicated the retention of acinar features but no expression of neuroendocrine markers (NSE, synaptophysin, chromogranin, and CD56), corresponding to nonelevated serum NSE...
April 13, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29600194/function-of-tumor-suppressors-in-resistance-to-antiandrogen-therapy-and-luminal-epithelial-plasticity-of-aggressive-variant-neuroendocrine-prostate-cancers
#17
REVIEW
Rama Soundararajan, Ana M Aparicio, Christopher J Logothetis, Sendurai A Mani, Sankar N Maity
Combined loss of tumor suppressors (TSPs), PTEN, TP53, and RB1, is highly associated with small cell carcinoma of prostate phenotype. Recent genomic studies of human tumors as well as analyses in mouse genetic models have revealed a unique role for these TSPs in dictating epithelial lineage plasticity-a phenomenon that plays a critical role in the development of aggressive variant prostate cancer (PCa) and associated androgen therapy resistance. Here, we summarize recently published key observations on this topic and hypothesize a possible mechanism by which concurrent loss of TSPs could potentially regulate the PCa disease phenotype...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29569310/molecular-model-for-neuroendocrine-prostate-cancer-progression
#18
REVIEW
Ruiqi Chen, Xuesen Dong, Martin Gleave
Prostate cancer (PCa) is the most common form of cancer for men in the developed world and the second leading cause of cancer-related deaths. While advanced PCa is initially controlled with hormonal therapies targeting the androgen receptor (AR) pathway, recurrence occurs due to the emergence of lethal castration-resistant PCa (CRPC). Despite newer AR pathway inhibitors that prolong survival, resistance still emerges, most often with rising PSA indicative of AR-driven activity, but increasingly as non-AR-driven cancer...
March 22, 2018: BJU International
https://www.readbyqxmd.com/read/29565650/recent-advances-in-theranostics-and-challenges-for-the-future
#19
J Harvey Turner
Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging...
March 29, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29559559/anaplastic-lymphoma-kinase-mutation-alk-f1174c-in-small-cell-carcinoma-of-the-prostate-and-molecular-response-to-alectinib
#20
Benedito A Carneiro, Sahithi Pamarthy, Ami N Shah, Vinay Sagar, Kenji Unno, HuiYing Han, Ximing J Yang, Rubens B Costa, Rebecca J Nagy, Richard B Lanman, Timothy M Kuzel, Jeffrey S Ross, Laurie Gay, Julia A Elvin, Siraj M Ali, Massimo Cristofanilli, Young K Chae, Francis J Giles, Sarki A Abdulkadir
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C-activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA)...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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