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neuroendocrine prostate cancer

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https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#1
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...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#2
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28402333/maoa-a-novel-decision-maker-of-apoptosis-and-autophagy-in-hormone-refractory-neuroendocrine-prostate-cancer-cells
#3
Yi-Cheng Lin, Yi-Ting Chang, Mel Campbell, Tzu-Ping Lin, Chin-Chen Pan, Hsin-Chen Lee, Jean C Shih, Pei-Ching Chang
Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate. An understanding of decision-making between these two pathways is in its infancy. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in psychiatric research. Emerging reports showed that overexpression MAOA is associated with prostate cancer (PCa). Here, we show that MAOA is involved in mediating neuroendocrine differentiation of PCa cells, a feature associated with hormone-refractory PCa (HRPC), a lethal type of disease...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382513/rna-splicing-and-splicing-regulator-changes-in-prostate-cancer-pathology
#4
REVIEW
Jennifer Munkley, Karen Livermore, Prabhakar Rajan, David J Elliott
Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA...
April 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/28361223/emerging-variants-of-castration-resistant-prostate-cancer
#5
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
#6
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...
March 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#7
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
https://www.readbyqxmd.com/read/28287131/separation-of-nuclear-isomers-for-cancer-therapeutic-radionuclides-based-on-nuclear-decay-after-effects
#8
R Bhardwaj, A van der Meer, S K Das, M de Bruin, J Gascon, H T Wolterbeek, A G Denkova, P Serra-Crespo
(177)Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β(-) emission results in very efficient energy deposition in small-size tumours. Because of this, (177)Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, (177m)Lu and (177)Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28285791/immunohistochemical-study-of-the-neural-development-transcription-factors-ttf1-ascl1-and-brn2-in-neuroendocrine-prostate-tumours
#9
E Rodríguez-Zarco, A Vallejo-Benítez, S Umbría-Jiménez, S Pereira-Gallardo, S Pabón-Carrasco, A Azueta, R González-Cámpora, P S Espinal, A García-Escudero
OBJECTIVE: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate...
March 9, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28256535/rest-is-a-crucial-regulator-for-acquiring-emt-like-and-stemness-phenotypes-in-hormone-refractory-prostate-cancer
#10
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/28247216/antitumor-activity-of-interferon-%C3%AE-1a-in-hormone-refractory-prostate-cancer-with-neuroendocrine-differentiation
#11
A Dicitore, E S Grassi, M O Borghi, G Gelmini, M C Cantone, G Gaudenzi, L Persani, M Caraglia, G Vitale
PURPOSE: Type I interferons (IFN-α and IFN-β) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-β showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-β products, such as IFN-β1a and IFN-β1b, have been produced in order to improve the stability and bioavailability of natural IFN-β...
March 1, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28243543/development-and-validation-of-a-36-gene-sequencing-assay-for-hereditary-cancer-risk-assessment
#12
Valentina S Vysotskaia, Gregory J Hogan, Genevieve M Gould, Xin Wang, Alex D Robertson, Kevin R Haas, Mark R Theilmann, Lindsay Spurka, Peter V Grauman, Henry H Lai, Diana Jeon, Genevieve Haliburton, Matt Leggett, Clement S Chu, Kevin Iori, Jared R Maguire, Kaylene Ready, Eric A Evans, Hyunseok P Kang, Imran S Haque
The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers...
2017: PeerJ
https://www.readbyqxmd.com/read/28240661/molecular-imaging-in-neuroendocrine-differentiation-of-prostate-cancer-68ga-psma-versus-68ga-dota-noc-pet-ct
#13
Sharjeel Usmani, Najeeb Ahmed, Fahad Marafi, Rashid Rasheed, Henney G Amanguno, Fareeda Al Kandari
We report on a 62-year-old man with metastatic prostate cancer (cT3b N1) diagnosed in 2011, treated with total androgen blockage with flutamide and goserelin acetate (Zoladex). He presented with left suprascapular swelling and low-back pain after being asymptomatic for 5 years. His prostate-specific antigen was 0.049 ng/mL. F-NaF PET-CT and Ga-PSMA scan were negative, whereas Ga-DOTA NOC scan done after 10 days showed multiple somatostatin-avid hepatic and lymph node metastasis.
May 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#14
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28194370/peptide-agonists-of-vasopressin-v2-receptor-reduce-expression-of-neuroendocrine-markers-and-tumor-growth-in-human-lung-and-prostate-tumor-cells
#15
Marina Pifano, Juan Garona, Carla S Capobianco, Nazareno Gonzalez, Daniel F Alonso, Giselle V Ripoll
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28178640/a-phase-i-ii-study-of-the-investigational-drug-alisertib-in-combination-with-abiraterone-and-prednisone-for-patients-with-metastatic-castration-resistant-prostate-cancer-progressing-on-abiraterone
#16
Jianqing Lin, Sheel A Patel, Ashwin R Sama, Jean H Hoffman-Censits, Brooke Kennedy, Deborah Kilpatrick, Zhong Ye, Hushan Yang, Zhaomei Mu, Benjamin Leiby, Nancy Lewis, Massimo Cristofanilli, William Kevin Kelly
LESSONS LEARNED: Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. BACKGROUND: We hypothesized that Aurora A kinase (AK) contributes to castrate resistance in prostate cancer (PCa) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor (AR) inhibitor abiraterone...
November 2016: Oncologist
https://www.readbyqxmd.com/read/28159676/transformation-of-prostatic-adenocarcinoma-to-well-differentiated-neuroendocrine-tumor-after-hormonal-treatment
#17
Syed Gilani, Charles C Guo, Elsa M Li-Ning, Curtis Pettaway, Patricia Troncoso
Carcinoid tumor of the prostate is extremely rare. Here we report a unique case of prostate cancer that underwent complete transformation from conventional adenocarcinoma to carcinoid-like tumor shortly after androgen deprivation treatment (ADT). The patient was a 59years old man who presented with lower urinary tract symptoms. His biopsy specimen demonstrated a high-grade prostatic adenocarcinoma with mixed acinar and ductal features. After ADT for 6months, the patient underwent radical prostatectomy. The post-ADT tumor showed monotonous neoplastic cells with fine granular chromatin forming rosette-like structures, resembling a carcinoid tumor...
January 31, 2017: Human Pathology
https://www.readbyqxmd.com/read/28152543/asporin-is-a-stromally-expressed-marker-associated-with-prostate-cancer-progression
#18
Annie Rochette, Nadia Boufaied, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Hayley C Whitaker, Antonio Ramos-Montoya, David E Neal, Alice Dragomir, Armen Aprikian, Simone Chevalier, Axel A Thomson
BACKGROUND: Prostate cancer shows considerable heterogeneity in disease progression and we propose that markers expressed in tumour stroma may be reliable predictors of aggressive tumour subtypes. METHODS: We have used Kaplan-Meier, univariate and multivariate analysis to correlate the expression of Asporin (ASPN) mRNA and protein with prostate cancer progression in independent cohorts. We used immunohistochemistry and H scoring to document stromal localisation of ASPN in a tissue microarray and mouse prostate cancer model, and correlated expression with reactive stroma, defined using Masson Trichrome staining...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28145883/therapy-induced-developmental-reprogramming-of-prostate-cancer-cells-and-acquired-therapy-resistance
#19
Mannan Nouri, Josselin Caradec, Amy Anne Lubik, Na Li, Brett G Hollier, Mandeep Takhar, Manuel Altimirano-Dimas, Mengqian Chen, Mani Roshan-Moniri, Miriam Butler, Melanie Lehman, Jennifer Bishop, Sarah Truong, Shih-Chieh Huang, Dawn Cochrane, Michael Cox, Colin Collins, Martin Gleave, Nicholas Erho, Mohamed Alshalafa, Elai Davicioni, Colleen Nelson, Sheryl Gregory-Evans, R Jeffrey Karnes, Robert B Jenkins, Eric A Klein, Ralph Buttyan
Treatment-induced neuroendocrine transdifferentiation (NEtD) complicates therapies for metastatic prostate cancer (PCa). Based on evidence that PCa cells can transdifferentiate to other neuroectodermally-derived cell lineages in vitro, we proposed that NEtD requires first an intermediary reprogramming to metastable cancer stem-like cells (CSCs) of a neural class and we demonstrate that several different AR+/PSA+ PCa cell lines were efficiently reprogrammed to, maintained and propagated as CSCs by growth in androgen-free neural/neural crest (N/NC) stem medium...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28109910/induction-of-neuroendocrine-differentiation-in-castration-resistant-prostate-cancer-cells-by-adipocyte-differentiation-related-protein-adrp-delivered-by-exosomes
#20
Li-Chiung Lin, Allen C Gao, Chih-Ho Lai, Jer-Tsong Hsieh, Ho Lin
Although overall mortality rate of prostate cancer (PCa) declines in recent years, castration-resistant prostate cancer (CRPC) remains incurable. Clinical evidence indicates that CRPC recurred from hormonal therapy exhibits neuroendocrine differentiated (NED) phenotypes, which could contribute to therapeutic resistance and poor survival. Understanding the onset of NED could lead us to develop new therapeutic strategies for CRPC. Although PCa is known as a lipid-enriched tumor, its role in CRPC development is not fully understood...
January 18, 2017: Cancer Letters
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