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CTC AND prostate cancer

Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Lori E Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M Piaseczny, Freeman Paczkowski, Alison L Allan
Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis...
October 15, 2016: Oncotarget
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
Silvin P Knight, Jacinta E Browne, James F Meaney, David S Smith, Andrew J Fagan
A novel anthropomorphic flow phantom device has been developed, which can be used for quantitatively assessing the ability of magnetic resonance imaging (MRI) scanners to accurately measure signal/concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data...
October 3, 2016: Physics in Medicine and Biology
Glenn Heller, Karim Fizazi, Robert T McCormack, Arturo Molina, David MacLean, Iain J Webb, Fred Saad, Johann S de Bono, Howard I Scher
PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from CRPC patients. Experimental Technique: Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
William L Harryman, James P Hinton, Cynthia P Rubenstein, Parminder Singh, Raymond B Nagle, Sarah J Parker, Beatrice S Knudsen, Anne E Cress
A critical barrier for the successful prevention and treatment of recurrent prostate cancer is detection and eradication of metastatic and therapy-resistant disease. Despite the fall in diagnoses and mortality, the reported incidence of metastatic disease has increased 72% since 2004. Prostate cancer arises in cohesive groups as intraepithelial neoplasia, migrates through muscle and leaves the gland via perineural invasion for hematogenous dissemination. Current technological advances have shown cohesive-clusters of tumor (also known as microemboli) within the circulation...
September 24, 2016: Biochimica et Biophysica Acta
Tilman Todenhöfer, Emily Sunyong Park, Simon Duffy, Xiaoyan Deng, Chao Jin, Hamidreza Abdi, Hongshen Ma, Peter C Black
BACKGROUND: Circulating tumor cells (CTC) have become an important tool in the monitoring of patients with advanced prostate cancer (PC). The role of CTC in localized disease has been addressed by only few studies. However, results of CTC analyses are strongly dependent on the platform used for CTC enrichment and detection. In the present study, a microfluidic platform allowing for antigen-independent enrichment of CTC was investigated for its ability to detect CTC in patients with clinically localized PC...
September 19, 2016: Urologic Oncology
Tobias M Gorges, Andra Kuske, Katharina Röck, Oliver Mauermann, Volkmar Müller, Sven Peine, Karl Verpoort, Vendula Novosadova, Mikael Kubista, Sabine Riethdorf, Klaus Pantel
BACKGROUND: Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS: CTCs were enriched based on their EpCAM expression (CellSearch®) or by size and deformability (Parsortix™), identified by EpCAM and/or pan-keratin-specific antibodies, and isolated for single cell multiplex RNA profiling. RESULTS: Distinct breast and prostate CTC expression signatures could be discriminated from RNA profiles of leukocytes...
September 14, 2016: Clinical Chemistry
Andrew S McDaniel, Roberta Ferraldeschi, Rachel Krupa, Mark Landers, Ryon Graf, Jessica Louw, Adam Jendrisak, Natalee Bales, Dena Marrinucci, Zafeiris Zafeiriou, Penelope Flohr, Spyridon Sideris, Joaquin Mateo, Johann S de Bono, Ryan Dittamore, Scott A Tomlins, Gerhardt Attard
OBJECTIVES: To utilize a non-biased assay of circulating tumour cells (CTCs) in prostate cancer (PCa) patients in order to identify non-traditional CTC phenotypes potentially excluded by conventional detection methods reliant upon antigen and/or sized based enrichment. PATIENTS AND METHODS: 41 metastatic castration resistant prostate cancer (mCRPC) patients and 20 healthy volunteers were analysed on the Epic CTC Platform, via high throughput imaging of DAPI expression and CD45/cytokeratin (CK) immunofluorescence (IF) in all circulating nucleated cells plated on glass slides...
August 18, 2016: BJU International
Yafeng Ma, Alison Luk, Francis P Young, David Lynch, Wei Chua, Bavanthi Balakrishnar, Paul de Souza, Therese M Becker
Androgen receptor splice variant V7 (AR-V7) was recently identified as a valuable predictive biomarker in metastatic castrate-resistant prostate cancer. Here, we report a new, sensitive and accurate screen for AR-V7 mRNA expression directly from circulating tumor cells (CTCs): We combined EpCAM-based immunomagnetic CTC isolation using the IsoFlux microfluidic platform with droplet digital polymerase chain reaction (ddPCR) to analyze total AR and AR-V7 expression from prostate cancer patients CTCs. We demonstrate that AR-V7 is reliably detectable in enriched CTC samples with as little as five CTCs, even considering tumor heterogeneity, and confirm detection of AR-V7 in CTC samples from advanced prostate cancer (PCa) patients with AR-V7 detection limited to castrate resistant disease status in our sample set...
2016: International Journal of Molecular Sciences
Nicholas J Vogelzang, Karim Fizazi, John M Burke, Ronald De Wit, Joaquim Bellmunt, Thomas E Hutson, Edward Crane, William R Berry, Kevin Doner, John D Hainsworth, Pawel J Wiechno, Kejian Liu, Michelle F Waldman, Anita Gandhi, Debora Barton, Ulf Jungnelius, Abderrahim Fandi, Cora N Sternberg, Daniel P Petrylak
: Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients...
August 10, 2016: European Urology
Gerit Theil, Kersten Fischer, Ekkehard Weber, Rita Medek, Raschid Hoda, Klaus Lücke, Paolo Fornara
BACKGROUND AND METHODS: Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized...
2016: PloS One
Christof Bernemann, Thomas J Schnoeller, Manuel Luedeke, Konrad Steinestel, Martin Boegemann, Andres J Schrader, Julie Steinestel
: The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC). Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide...
July 25, 2016: European Urology
Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J Eigl, Martin E Gleave, Anthony M Joshua, Peter C Black, Kim N Chi
PURPOSE: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts...
July 17, 2016: Journal of Urology
Miriam Hegemann, Arnulf Stenzl, Jens Bedke, Kim Nguyen Chi, Peter Colin Black, Tilman Todenhöfer
The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalized treatment strategies in patients with metastatic prostate cancer (PC). Only in a low proportion of patients, biopsies of metastatic tissue are performed. Circulating tumor cells (CTC), cell free-DNA (cfDNA) and RNA offer the potential for non-invasive characterization of disease and molecular stratification of patients. Furthermore, a "liquid biopsy" approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes...
July 19, 2016: BJU International
Emma Pailler, Marianne Oulhen, Fanny Billiot, Alexandre Galland, Nathalie Auger, Vincent Faugeroux, Corinne Laplace-Builhé, Benjamin Besse, Yohann Loriot, Maud Ngo-Camus, Merouan Hemanda, Colin R Lindsay, Jean-Charles Soria, Philippe Vielh, Françoise Farace
BACKGROUND: Circulating tumor cell (CTC)-filtration methods capture high numbers of CTCs in non-small-cell lung cancer (NSCLC) and metastatic prostate cancer (mPCa) patients, and hold promise as a non-invasive technique for treatment selection and disease monitoring. However filters have drawbacks that make the automation of microscopy challenging. We report the semi-automated microscopy method we developed to analyze filtration-enriched CTCs from NSCLC and mPCa patients. METHODS: Spiked cell lines in normal blood and CTCs were enriched by ISET (isolation by size of epithelial tumor cells)...
2016: BMC Cancer
Jame M Sperger, Lindsay N Strotman, Allison Welsh, Benjamin P Casavant, Zachary Chalmers, Sacha Horn, Erika Heninger, Stephanie Thiede, Jacob Tokar, Benjamin K Gibbs, David J Guckenberger, Lakeesha Carmichael, Scott M Dehm, Philip J Stephens, David J Beebe, Scott M Berry, Joshua M Lang
PURPOSE: There is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (Versatile Exclusion-based Rare Sample Analysis) was developed to integrate readouts across protein, mRNA and DNA in Circulating Tumor Cells (CTCs) for a comprehensive analysis of the Androgen Receptor (AR) signaling pathway. EXPERIMENTAL DESIGN: Utilizing exclusion based sample preparation principles, a handheld chip was developed to perform CTC capture, enumeration, quantification and subcellular localization of proteins and extraction of mRNA and DNA...
July 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Matthew Smith, Johann De Bono, Cora Sternberg, Sylvestre Le Moulec, Stéphane Oudard, Ugo De Giorgi, Michael Krainer, Andries Bergman, Wolfgang Hoelzer, Ronald De Wit, Martin Bögemann, Fred Saad, Giorgio Cruciani, Antoine Thiery-Vuillemin, Susan Feyerabend, Kurt Miller, Nadine Houédé, Syed Hussain, Elaine Lam, Jonathan Polikoff, Arnulf Stenzl, Paul Mainwaring, David Ramies, Colin Hessel, Aaron Weitzman, Karim Fizazi
PURPOSE: Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Christophe Massard, Marianne Oulhen, Sylvestre Le Moulec, Nathalie Auger, Stéphanie Foulon, Aurélie Abou-Lovergne, Fanny Billiot, Alexander Valent, Virginie Marty, Yohann Loriot, Karim Fizazi, Philippe Vielh, Francoise Farace
Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively...
July 4, 2016: Oncotarget
Jie-Fu Chen, Yazhen Zhu, Yi-Tsung Lu, Elisabeth Hodara, Shuang Hou, Vatche G Agopian, James S Tomlinson, Edwin M Posadas, Hsian-Rong Tseng
Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients...
2016: Theranostics
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