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https://www.readbyqxmd.com/read/28819021/phenotypic-heterogeneity-of-circulating-tumor-cells-informs-clinical-decisions-between-ar-signaling-inhibitors-and-taxanes-in-metastatic-prostate-cancer
#1
Howard I Scher, Ryon P Graf, Nicole Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica Louw, Lyndsey Dugan, Hebert Alberto Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan V Dittamore
The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818355/ar-v7-in-peripheral-whole-blood-of-patients-with-castration-resistant-prostate-cancer-association-with-treatment-specific-outcome-under-abiraterone-and-enzalutamide
#2
Anna Katharina Seitz, Silvia Thoene, Andreas Bietenbeck, Roman Nawroth, Robert Tauber, Mark Thalgott, Sebastian Schmid, Ramona Secci, Margitta Retz, Jürgen E Gschwend, Jürgen Ruland, Christof Winter, Matthias M Heck
BACKGROUND: It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. OBJECTIVE: To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients...
August 14, 2017: European Urology
https://www.readbyqxmd.com/read/28809987/label-free-ferrohydrodynamic-cell-separation-of-circulating-tumor-cells
#3
Wujun Zhao, Rui Cheng, Brittany D Jenkins, Taotao Zhu, Nneoma E Okonkwo, Courtney E Jones, Melissa B Davis, Sravan K Kavuri, Zhonglin Hao, Carsten Schroeder, Leidong Mao
Circulating tumor cells (CTCs) have significant implications in both basic cancer research and clinical applications. To address the limited availability of viable CTCs for fundamental and clinical investigations, effective separation of extremely rare CTCs from blood is critical. Ferrohydrodynamic cell separation (FCS), a label-free method that conducted cell sorting based on cell size difference in biocompatible ferrofluids, has thus far not been able to enrich low-concentration CTCs from cancer patients' blood because of technical challenges associated with processing clinical samples...
August 15, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28753792/interrogating-metastatic-prostate-cancer-treatment-switch-decisions-a-multi-institutional-survey
#4
David Lorente, Praful Ravi, Niven Mehra, Carmel Pezaro, Aurelius Omlin, Alexa Gilman, Miguel Miranda, Pasquale Rescigno, Michael Kolinsky, Nuria Porta, Diletta Bianchini, Nina Tunariu, Raquel Perez, Joaquin Mateo, Heather Payne, Leon Terstappen, Maarten IJzerman, Emma Hall, Johann de Bono
BACKGROUND: Evaluation of responses to treatment for metastatic castration-resistant prostate cancer (mCRPC) remains challenging. Consensus criteria based on prostate-specific antigen (PSA) and clinical and radiologic biomarkers are inconsistently utilized. Circulating tumor cell (CTC) counts can inform prognosis and response, but are not routinely used. OBJECTIVE: To evaluate the use of biomarkers and trends in clinical decision-making in current mCRPC treatment...
October 10, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28670371/circulating-tumor-cells-what-we-know-what-do-we-want-to-know-about-them-and-are-they-ready-to-be-used-in-clinics
#5
Zuzana Bielčiková, Anna Jakabová, Michael Pinkas, Milada Zemanová, Katarína Kološtová, Vladimír Bobek
Circulating tumor cells (CTC) present in peripheral blood are assigned precursors of advanced tumor disease. Simplicity of blood withdrawal procedure adds practically an unlimited possibility of the CTC-monitoring and the advantages of the repeated biopsies over time. CTC got prognostic, predictive and diagnostic status with the technologic advance. Although the clinical utility of CTC has reached the high evidence, the significance of CTC testing was presented in the treatment strategy mostly with palliative intention...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28668277/a-phase-ii-trial-of-aezs-108-in-castration-and-taxane-resistant-prostate-cancer
#6
Steven S Yu, Kanthi Athreya, Stephen V Liu, Andrew V Schally, Denice Tsao-Wei, Susan Groshen, David I Quinn, Tanya B Dorff, Shigang Xiong, Jurgen Engel, Jacek Pinski
BACKGROUND: AEZS-108 (zoptarelin doxorubicin) is a cytotoxic hybrid molecule consisting of doxorubicin covalently coupled with a luteinizing hormone-releasing hormone (LHRH) analogue, which selectively targets doxorubicin to tumor cells expressing LHRH receptors. We report the clinical efficacy of AEZS-108 in a phase II trial in men with metastatic castrate-resistant prostate cancer who had disease progression after taxane-based chemotherapy. PATIENTS AND METHODS: Patients received AEZS-108 210 mg/m(2) intravenously every 3 weeks...
June 8, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#7
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28615267/the-novel-association-of-circulating-tumor-cells-and-circulating-megakaryocytes-with-prostate-cancer-prognosis
#8
Lei Xu, Xueying Mao, Tianyu Guo, Pui Ying Chan, Greg Shaw, John Hines, Elzbieta Stankiewicz, Yuqin Wang, R Tim D Oliver, Amar Sabri Ahmad, Daniel Berney, Jonathan Shamash, Yong-Jie Lu
To develop an approach for the investigation of different subtypes of circulating tumor cells (CTCs) and other cells to evaluate their potential prognostic value of prostate cancer.<br /><br />Experimental Design: Malignancy of CTCs undergoing epithelial to mesenchymal transition (EMT) was confirmed by repeated Fluorescence in situ hybridization. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28589907/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#9
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560677/mesenchymal-epithelial-transition-and-circulating-tumor-cells-in-small-cell-lung-cancer
#10
Gerhard Hamilton, Barbara Rath
Cancer patients die of metastatic disease but knowledge regarding individual steps of this complex process of intravasation, spread and extravasation leading to secondary lesions is incomplete. Subpopulations of tumor cells are supposed to undergo an epithelial-mesenchymal transition (EMT), to enter the bloodstream and eventually establish metastases in a reverse process termed mesenchymal-epithelial transition (MET). Small cell lung cancer (SCLC) represents a unique model to study metastatic spread due to early dissemination and relapse, as well as availability of a panel of circulating cancer cell (CTC) lines recently...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28560675/enrichment-isolation-and-molecular-characterization-of-epcam-negative-circulating-tumor-cells
#11
Rita Lampignano, Helen Schneck, Martin Neumann, Tanja Fehm, Hans Neubauer
The presence of EpCAM-positive circulating tumor cells (CTCs) in the peripheral blood is associated with poor clinical outcomes in breast, colorectal and prostate cancer, as well as the prognosis of other tumor types. In addition, recent studies have suggested that the presence of CTCs undergoing epithelial-to-mesenchymal transition and, as such, may exhibit reduced or no expression of epithelial proteins e.g. EpCAM, might be related to disease progression in metastatic breast cancer (MBC) patients. Analyzing the neoplastic nature of this EpCAM-low/negative (EpCAM-neg) subpopulation remains an open issue as the current standard detection methods for CTCs are not efficient at identifying this subpopulation of cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28529342/circulating-tumor-cells-and-serum-levels-of-mmp-2-mmp-9-and-vegf-as-markers-of-the-metastatic-process-in-patients-with-high-risk-of-metastatic-progression
#12
Marketa Skerenova, Veronika Mikulova, Otakar Capoun, Tomas Zima, Petra Tesarova
BACKGROUND AND AIMS: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients...
May 16, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28521303/emt-circulating-tumor-cells-detected-by-cell-surface-vimentin-are-associated-with-prostate-cancer-progression
#13
Arun Satelli, Izhar Batth, Zachary Brownlee, Abhishek Mitra, Shouhao Zhou, Hyangsoon Noh, Christina R Rojas, Heming Li, Qing H Meng, Shulin Li
Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498319/ctc-mrna-ar-v7-analysis-from-blood-samples-impact-of-blood-collection-tube-and-storage-time
#14
Alison W S Luk, Yafeng Ma, Pei N Ding, Francis P Young, Wei Chua, Bavanthi Balakrishnar, Daniel T Dransfield, Paul de Souza, Therese M Becker
Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer biomarkers. New technologies for CTC isolation and biomarker detection are increasingly sensitive, however, the ideal blood storage conditions to preserve CTC-specific mRNA biomarkers remains undetermined. Here we tested the preservation of tumour cells and CTC-mRNA over time in common anticoagulant ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B (Citrate) blood tubes compared to preservative-containing blood tubes...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28456090/dynamic-evaluation-of-circulating-tumour-cells-in-patients-with-advanced-gastric-and-oesogastric-junction-adenocarcinoma-prognostic-value-and-early-assessment-of-therapeutic-effects
#15
Simon Pernot, Cecile Badoual, Magali Terme, Florence Castan, Aurelie Cazes, Olivier Bouche, Jaafar Bennouna, Eric Francois, Francois Ghiringhelli, Christelle De La Fouchardiere, Emmanuelle Samalin, Jean Baptiste Bachet, Christophe Borg, Michel Ducreux, Elie Marcheteau, Trevor Stanbury, Sophie Gourgou, David Malka, Julien Taieb
BACKGROUND: The identification of dynamic biomarkers in advanced gastric and oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to establish the optimal threshold and the clinical significance of CTC count in advanced GOA before and during treatment. METHODS: One hundred six patients with untreated advanced GOA were included in the ancillary study of the PRODIGE 17-ACCORD 20 trial...
April 26, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28427756/human-tissue-kallikreins-blood-levels-and-response-to-radiotherapy-in-intermediate-risk-prostate-cancer
#16
Nicola J Nasser, John Thoms, Antoninus Soosaipillai, Melania Pintilie, Ri Wang, Eleftherios P Diamandis, Robert G Bristow
OBJECTIVES: Kallikreins are serine proteases over expressed in many malignancies. In this study, we measure changes in serum kallikrein (KLKs) levels during intensity-modulated radiotherapy (IMRT) in prostate cancer patients, and find potential correlations between serum kallikrein level and normal tissues toxicity during radiation. METHODS: Forty-nine patients with prostate cancer were recruited as follows: group 1, definitive standard fractionation IMRT (78Gy in 39 fractions, n=15); group 2, definitive hypofractionated IMRT (60Gy in 20 fractions, n=15); and group 3, IMRT postprostatectomy (66Gy in 33 fractions, n=19)...
April 17, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28427152/radioligand-therapy-of-metastatic-prostate-cancer-using-177lu-psma-617-after-radiation-exposure-to-223ra-dichloride
#17
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with 177Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with 223Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of 177Lu-PSMA-617 after exposure to more cycles of 223Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with 223Ra...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425472/label-free-single-cell-separation-and-imaging-of-cancer-cells-using-an-integrated-microfluidic-system
#18
Maria Antfolk, Soo Hyeon Kim, Saori Koizumi, Teruo Fujii, Thomas Laurell
The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#19
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28384066/clinical-significance-of-androgen-receptor-splice-variant-7-mrna-detection-in-circulating-tumor-cells-of-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-first-and-second-line-abiraterone-and-enzalutamide
#20
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L Silberstein, Maritza N Taylor, Benjamin L Maughan, Samuel R Denmeade, Kenneth J Pienta, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Jun Luo
Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay...
July 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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