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Circulating tumor cells in prostate cancer

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https://www.readbyqxmd.com/read/29474983/an-in-depth-evaluation-of-the-validity-and-logistics-surrounding-the-testing-of-ar-v7-mrna-expression-in-circulating-tumor-cells
#1
Anieta M Sieuwerts, Bianca Mostert, Michelle van der Vlugt-Daane, Jaco Kraan, Corine Beaufort, Mai Van, Wendy J C Prager, Bram De Laere, Nick Beije, Paul Hamberg, Hans M Westgeest, Metin Tascilar, Luc Y Dirix, Wendy Onstenk, Ronald de Wit, Martijn P Lolkema, Ron H J Mathijssen, John W M Martens, Stefan Sleijfer
Recent reports have emphasized the clinical relevance of detecting the androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs). Our aim was to set up a validated multicenter pipeline to measure AR-V7 by RT-qPCR in RNA isolated from CellSearch-enriched CTCs to provide an AR-V7 positive/negative score in a clinically acceptable time range. CellSearch-enirched CTCs from metastatic castration-resistant prostate cancer patients were characterized by RT-qPCR. After optimization it was prospectively tested whether it was possible to report the AR-V7 status within 11 days (PRELUDE study)...
February 20, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29470068/a-potent-epha2-agonistic-peptide-drug-conjugate-reduces-circulating-cancer-cells-and-metastases-in-breast-cancer-models
#2
Ahmed F Salem, Si Wang, Sandrine Billet, Jie-Fu Chen, Parima Udompholkul, Luca Gambini, Carlo Baggio, Hsian-Rong Tseng, Edwin M Posadas, Neil A Bhowmick, Maurizio Pellecchia
EphA2 overexpression has been associated with metastasis of multiple cancer types, including melanoma, ovarian, prostate, lung, and breast cancer. We have recently proposed to develop peptide-drug conjugates (PDCs) using agonistic EphA2-targeting agents such as the YSA peptide or its optimized version 123B9. While our studies indicated that YSA- or 123B9-drug conjugates can selectively deliver cytotoxic drugs to cancer cells in vivo, the relatively low cellular agonistic activity (high micromolar) of the agents for the EphA2 receptor remained a limiting factor to warrant further development of these PDCs in the clinic...
February 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29464943/molecular-profiling-of-pooled-circulating-tumor-cells-from-prostate-cancer-patients-using-dual-antibody-functionalized-microfluidic-device
#3
Changqing Yin, Yuhui Wang, Jia Ji, Bo Cai, Hao Chen, Zhonghua Yang, Kun Wang, Changliang Luo, Wu-Wen Zhang, Chunhui Yuan, Fubing Wang
Here, we constructed a novel dual-antibody-functionalized microfluidic device by employing antibodies against PSMA and EpCAM to capture CTCs from PCa patients in order to capture multiple subpopulations of CTCs at different metastatic stages. In vitro experiments with dual capture system for capturing both LnCAP and LnCAP-EMT cells have shown significantly enhanced capture efficiency as compared to that of EpCAM single capture system. Furthermore, dual capture system could successfully identify CTCs in 20 out of 24 (83...
February 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#4
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29445099/pharmacokinetic-pharmacodynamic-correlations-in-the-development-of-ginger-extract-as-an-anticancer-agent
#5
Rao Mukkavilli, Chunhua Yang, Reenu Singh Tanwar, Roopali Saxena, Sushma R Gundala, Yingyi Zhang, Ahmed Ghareeb, Stephan D Floyd, Subrahmanyam Vangala, Wei-Wen Kuo, Padmashree C G Rida, Ritu Aneja
Anticancer efficacy of ginger phenolics (GPs) has been demonstrated in various in vitro assays and xenograft mouse models. However, only sub-therapeutic plasma concentrations of GPs were detected in human and mouse pharmacokinetic (PK) studies. Intriguingly, a significant portion of GPs occurred as phase II metabolites (mainly glucuronide conjugates) in plasma. To evaluate the disposition of GPs and understand the real players responsible for efficacy, we performed a PK and tissue distribution study in mice...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29434856/high-fat-diet-induced-adipokine-and-cytokine-alterations-promote-the-progression-of-prostate-cancer-in-vivo-and-in-vitro
#6
Meng-Bo Hu, Hua Xu, Wen-Hui Zhu, Pei-De Bai, Ji-Meng Hu, Tian Yang, Hao-Wen Jiang, Qiang Ding
High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431639/cxcl12%C3%AE-%C3%A2-promotes-development-of-metastatic-castration-resistant-prostate-cancer-by-induction-of-cancer-stem-cell-and-neuroendocrine-phenotypes
#7
Younghun Jung, Frank C Cackowski, Kenji Yumoto, Ann Decker, Jingcheng Wang, Jinkoo Kim, Eunsohl Lee, Yugang Wang, Jae-Seung Chung, Amy M Gursky, Paul H Krebsbach, Kenneth J Pienta, Todd M Morgan, Russell S Taichman
There is evidence that cancer stem-like cells (CSC) and neuroendocrine (NE) behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limiting mechanistic understanding of how CSC and NE phenotypes impact the development of m-CRPC, which could improve opportunities to identify useful biomarkers and therapeutics. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and NE differentiation and its impact on m-CRPC...
February 5, 2018: Cancer Research
https://www.readbyqxmd.com/read/29431193/circulating-tumor-cells-and-survival-in-abiraterone-and-enzalutamide-treated-patients-with-castration-resistant-prostate-cancer
#8
Bram De Laere, Steffi Oeyen, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Piet Van Kerckhove, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge de Kruijff, Valerie van Dam, Anja Brouwer, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Stefan Sleijfer, Jean Vandebroek, Steven Van Laere, Luc Dirix
BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies...
February 12, 2018: Prostate
https://www.readbyqxmd.com/read/29400475/albumin-binding-psma-ligands-optimization-of-the-tissue-distribution-profile
#9
Martina Benešová, Christoph A Umbricht, Roger Schibli, Cristina Müller
The prostate-specific membrane antigen (PSMA) has emerged as an attractive prostate cancer associated target for radiotheragnostic application using PSMA-specific radioligands. The aim of this study was to design new PSMA ligands modified with an albumin-binding moiety in order to optimize their tissue distribution profile. The compounds were prepared by conjugation of a urea-based PSMA-binding entity, a DOTA chelator, and 4-(p-iodophenyl)butyric acid using multistep solid phase synthesis. The three ligands (PSMA-ALB-02, PSMA-ALB-05, and PSMA-ALB-07) were designed with varying linker entities...
February 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29367197/circulating-tumor-dna-genomics-correlate-with-resistance-to-abiraterone-and-enzalutamide-in-prostate-cancer
#10
Matti Annala, Gillian Vandekerkhove, Daniel Khalaf, Sinja Taavitsainen, Kevin Beja, Evan W Warner, Katherine Sunderland, Christian Kollmannsberger, Bernhard J Eigl, Daygen Finch, Conrad D Oja, Joanna Vergidis, Muhammad Zulfiqar, Arun A Azad, Matti Nykter, Martin E Gleave, Alexander W Wyatt, Kim N Chi
Primary resistance to androgen receptor (AR) directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 treatment-naive mCRPC patients to abiraterone or enzalutamide, and performed whole exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance...
January 24, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29361118/assessment-of-circulating-tumor-cells-as-a-predictive-biomarker-of-histology-in-women-with-suspected-ovarian-cancer
#11
Emil Lou, Rachel I Vogel, Deanna Teoh, Spencer Hoostal, Aaron Grad, Matthew Gerber, Minnu Monu, Tomasz Lukaszewski, Jaai Deshpande, Michael A Linden, Melissa A Geller
Background: The clinical assessment of circulating tumor cells (CTCs) as a blood-based biomarker is FDA-approved for use in breast, colorectal, and prostate cancers. The objective of this prospective clinical study was to determine whether pretreatment CTCs are a useful diagnostic biomarker in women with complex pelvic masses. Methods: Whole blood was collected from 49 women with newly diagnosed pelvic masses. The presence of CTCs was compared between women with and without ovarian cancer histopathologic diagnosis after surgery using a Chi-squared test...
January 19, 2018: Laboratory Medicine
https://www.readbyqxmd.com/read/29359890/performance-comparison-of-two-ar-v7-detection-methods
#12
Christof Bernemann, Julie Steinestel, Verena Humberg, Martin Bögemann, Andres Jan Schrader, Jochen K Lennerz
OBJECTIVES: Paradoxical responses to next-generation androgen deprivation therapy in AR-V7 mRNA-positive circulating tumor cells of castration-resistant prostate cancer patients could be related to false-positive classification using detection systems with different sensitivities. A performance comparison of the two established AR-V7 mRNA detection systems has not been performed. MATERIALS AND METHODS: Here, we report a performance comparison of two established mRNA-based AR-V7 detection technologies using either SYBR Green or TaqMan chemistries...
January 23, 2018: BJU International
https://www.readbyqxmd.com/read/29339080/prostate-cancer-disseminated-tumor-cells-are-rarely-detected-in-the-bone-marrow-of-localized-patients-undergoing-radical-prostatectomy-across-multiple-rare-cell-detection-platforms
#13
Heather J Chalfin, Stephanie A Glavaris, Paymaneh D Malihi, Jamie M Sperger, Michael A Gorin, Changxue Lu, C Rory Goodwin, Yan Chen, Emily A Caruso, Ruth Dumpit, Peter Kuhn, Joshua M Lang, Peter S Nelson, Jun Luo, Kenneth J Pienta
PURPOSE: Prostate circulating tumor cells escape into the peripheral blood and enter the bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease, and existing detection methods rely on epithelial markers with low specificity and sensitivity. Here we employed multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy. MATERIALS AND METHODS: Bone marrow was harvested from 208 clinically localized patients, 16 controls, and 5 metastatic patients, with peripheral blood from 37 metastatic patients...
January 12, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#14
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29301749/in-situ-detection-and-quantification-of-ar-v7-ar-fl-psa-and-kras-point-mutations-in-circulating-tumor-cells
#15
Amin El-Heliebi, Claudia Hille, Navya Laxman, Jessica Svedlund, Christoph Haudum, Erkan Ercan, Thomas Kroneis, Shukun Chen, Maria Smolle, Christopher Rossmann, Tomasz Krzywkowski, Annika Ahlford, Evangelia Darai, Gunhild von Amsberg, Winfried Alsdorf, Frank König, Matthias Löhr, Inge de Kruijff, Sabine Riethdorf, Tobias M Gorges, Klaus Pantel, Thomas Bauernhofer, Mats Nilsson, Peter Sedlmayr
BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs...
January 4, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29301747/an-rna-based-digital-circulating-tumor-cell-signature-is-predictive-of-drug-response-and-early-dissemination-in-prostate-cancer
#16
David T Miyamoto, Richard J Lee, Mark Kalinich, Joseph LiCausi, Yu Zheng, Tianqi Chen, John D Milner, Erin Emmons, Uyen Ho, Katherine Broderick, Erin Silva, Sarah Javaid, Tanya Todorova Kwan, Xin Hong, Douglas M Dahl, Francis J McGovern, Jason A Efstathiou, Matthew R Smith, Lecia V Sequist, Ravi Kapur, Chin-Lee Wu, Shannon L Stott, David T Ting, Anita Giobbie-Hurder, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber
Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTCs) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 metastatic castration-resistant prostate cancer patients treated with first-line abiraterone, pretreatment elevation of the digital CTCM Score identifies a high risk population with poor overall survival (HR 6...
January 4, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29289429/synaptophysin-expression-on-circulating-tumor-cells-in-patients-with-castration-resistant-prostate-cancer-undergoing-treatment-with-abiraterone-acetate-or-enzalutamide
#17
Sumanta K Pal, Miaoling He, Lin Chen, Lixin Yang, Raju Pillai, Przemyslaw Twardowski, JoAnn Hsu, Marcin Kortylewski, Jeremy O Jones
BACKGROUND: With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are becoming more prevalent. Many of these cancers express neuroendocrine markers, which may provide biomarkers for emergence of this disease state. We aimed to quantify the expression of synaptophysin (Syp) on circulating tumor cells (CTCs) from serial samples of patients being treated with abiraterone acetate or enzalutamide...
December 27, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29285777/analogous-detection-of-circulating-tumor-cells-using-the-accucyte-%C3%A2-cytefinder-%C3%A2-system-and-iset-system-in-patients-with-locally-advanced-and-metastatic-prostate-cancer
#18
Emma E van der Toom, Vincent P Groot, Stephanie A Glavaris, Georgios Gemenetzis, Heather J Chalfin, Laura D Wood, Christopher L Wolfgang, Jean J M C H de la Rosette, Theo M de Reijke, Kenneth J Pienta
INTRODUCTION: Circulating tumor cells (CTCs) can provide important information on patient's prognosis and treatment efficacy. Currently, a plethora of methods is available for the detection of these rare cells. We compared the outcomes of two of those methods to enumerate and characterize CTCs in patients with locally advanced and metastatic prostate cancer (PCa). First, the selection-free AccuCyte ® - CyteFinder ® system (RareCyte ® , Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size-exclusion...
March 2018: Prostate
https://www.readbyqxmd.com/read/29284359/rare-incidence-of-tumor-lysis-syndrome-in-metastatic-prostate-cancer-following-treatment-with-docetaxel
#19
Sharonlin Bhardwaj, Seema Varma
Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29260398/integrated-bioinformatics-analysis-of-potential-biomarkers-for-prostate-cancer
#20
Jiufeng Tan, Xuefei Jin, Kaichen Wang
The aim was to expound the pathogenesis of prostate cancer and to identify the potentially biomarkers for prostate cancer (PC). DNA methylation microarray data GSE38240 containing 8 prostate cancer metastases and 4 normal prostate samples as well as gene expression profile data GSE26910 containing 6 prostate primary tumors and 6 normal samples were used. Differentially expressed genes (DEGs) and differently methylated sites of PC were screened and the regulatory network was constructed with DEGs-related transcription factors (TFs)...
December 19, 2017: Pathology Oncology Research: POR
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