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neuroendocrine prostate cancer

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https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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-68-ga-psma-versus-68-ga-dota-noc-pet-ct
#7
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.
February 24, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
January 27, 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
#14
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
https://www.readbyqxmd.com/read/28108457/rb1-and-tp53-loss-promotes-lineage-plasticity-in-prostate-cancer
#15
(no author information available yet)
Loss of RB1 and TP53 induces a neuroendocrine phenotype that confers resistance to antiandrogen therapy.
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28103576/a-new-model-of-multi-visceral-and-bone-metastatic-prostate-cancer-with-perivascular-niche-targeting-by-a-novel-endothelial-specific-adenoviral-vector
#16
Zhi Hong Lu, Sergey Kaliberov, Rebecca E Sohn, Lyudmila Kaliberova, Yingqiu Du, Julie L Prior, Daniel J Leib, Anne Chauchereau, Jennifer K Sehn, David T Curiel, Jeffrey M Arbeit
While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation. Parallel work revealed that endothelial cells (ECs) create a perivascular CSC niche mediated by juxtacrine and membrane tethered signaling. There is increasing interest in pharmacological metastatic niche targeting, however, targeted access has been impossible...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059767/rb1-and-trp53-cooperate-to-suppress-prostate-cancer-lineage-plasticity-metastasis-and-antiandrogen-resistance
#17
Sheng Yu Ku, Spencer Rosario, Yanqing Wang, Ping Mu, Mukund Seshadri, Zachary W Goodrich, Maxwell M Goodrich, David P Labbé, Eduardo Cortes Gomez, Jianmin Wang, Henry W Long, Bo Xu, Myles Brown, Massimo Loda, Charles L Sawyers, Leigh Ellis, David W Goodrich
Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting that lineage plasticity facilitates therapeutic resistance. The mechanisms underlying prostate cancer lineage plasticity are incompletely understood. Studying mouse models, we demonstrate that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28054315/the-missing-link-in-the-diagnostic-pathway-of-prostate-cancer
#18
Arne Vidar Tind Wøyen, Gergely Laczkó, Søren Høyer, Laszlo Hegyi
Prostate cancer is one of the most common cancers in the Western world. It is among the leading causes of cancer related death. While its incidence and survival increased significantly during the last few decades in Denmark, the mortality rate did not change for patients younger than 80 year old. Development of new techniques, such as multiparametric MRI, helps to increase the accuracy of diagnosis. However, a missing link in the diagnostic pathway may result in mistreatment if an acinar adenocarcinoma of prostate is transformed into a neuroendocrine phenotype such as small cell carcinoma...
January 4, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28048586/th-ab-206-00-challenges-and-opportunities-for-nuclear-medicine-theranostics
#19
Osama Mawlawi
In the past few decades, the field of nuclear medicine has made long strides with the continued advancement of related sciences and engineering and the availability of diagnostic and therapeutic radionuclides. Leveraging these advancements while combining the advantages of therapeutic and diagnostic radionuclides into one radiopharmaceutical has also created a new subfield "theranostics" in nuclear medicine that has the potential to further propel the field into the future. This session is composed of two talks; one focused on the physics principles of theranostics from properties of beta and alpha emitting radionuclides to dosimetric models and quantification; while the second describes preclinical and clinical applications of theranostics and discusses the challenges and opportunities of bringing them to the clinic...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047028/th-ab-206-01-advances-in-radionuclide-therapy-from-radioiodine-to-nanoparticles
#20
J Humm
In the past few decades, the field of nuclear medicine has made long strides with the continued advancement of related sciences and engineering and the availability of diagnostic and therapeutic radionuclides. Leveraging these advancements while combining the advantages of therapeutic and diagnostic radionuclides into one radiopharmaceutical has also created a new subfield "theranostics" in nuclear medicine that has the potential to further propel the field into the future. This session is composed of two talks; one focused on the physics principles of theranostics from properties of beta and alpha emitting radionuclides to dosimetric models and quantification; while the second describes preclinical and clinical applications of theranostics and discusses the challenges and opportunities of bringing them to the clinic...
June 2016: Medical Physics
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