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circulating tumor cell cluster

Shakila Jabeen, Jaime A Espinoza, Lilly Anne Torland, Manuela Zucknick, Surendra Kumar, Vilde D Haakensen, Torben Lüders, Olav Engebraaten, Anne-Lise Børresen-Dale, Jon Amund Kyte, Pavel Gromov, Bjørn Naume, Vessela Kristensen, Irina Gromova, Xavier Tekpli
Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines - the molecules coordinating and fine-tuning immune response - are still poorly characterized. Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the levels of 27 cytokines in the serum of breast cancer patients prior to treatment...
2019: Oncoimmunology
Emilie Picard, Yann Godet, Caroline Laheurte, Magalie Dosset, Jeanne Galaine, Laurent Beziaud, Romain Loyon, Laura Boullerot, Elodie Lauret Marie Joseph, Laurie Spehner, Marion Jacquin, Guillaume Eberst, Béatrice Gaugler, Françoise Le Pimpec-Barthes, Elizabeth Fabre, Virginie Westeel, Anne Caignard, Christophe Borg, Olivier Adotévi
Natural killer (NK) cells are innate effector lymphocytes widely involved in cancer immunosurveillance. In this study, we described three circulating NK cell subsets in patients with non-small cell lung cancer (NSCLC). Compared to healthy donors (HD), lower rate of the cytotoxic CD56dim CD16+ NK cells was found in NSCLC patients (76.1% vs 82.4%, P  = 0.0041). In contrast, the rate of CD56bright NK cells was similar between patients and HD. We showed in NSCLC patients a higher rate of a NK cell subset with CD56dim CD16- phenotype (16...
2019: Oncoimmunology
Molly Kozminsky, Shamileh Fouladdel, Jae-Seung Chung, Yugang Wang, David C Smith, Ajjai Alva, Ebrahim Azizi, Todd Morgan, Sunitha Nagrath
Rates of progression and treatment response in advanced prostate cancer are highly variable, necessitating non-invasive methods to assess the molecular characteristics of these tumors in real time. The unique potential of circulating tumor cells (CTCs) to serve as a clinically useful liquid biomarker is due to their ability to inform via both enumeration and RNA expression. A microfluidic graphene oxide-based device (GO Chip) is used to isolate CTCs and CTC clusters from the whole blood of 41 men with metastatic castration-resistant prostate cancer...
January 23, 2019: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Sofia Gkountela, Francesc Castro-Giner, Barbara Maria Szczerba, Marcus Vetter, Julia Landin, Ramona Scherrer, Ilona Krol, Manuel C Scheidmann, Christian Beisel, Christian U Stirnimann, Christian Kurzeder, Viola Heinzelmann-Schwarz, Christoph Rochlitz, Walter Paul Weber, Nicola Aceto
The ability of circulating tumor cells (CTCs) to form clusters has been linked to increased metastatic potential. Yet biological features and vulnerabilities of CTC clusters remain largely unknown. Here, we profile the DNA methylation landscape of single CTCs and CTC clusters from breast cancer patients and mouse models on a genome-wide scale. We find that binding sites for stemness- and proliferation-associated transcription factors are specifically hypomethylated in CTC clusters, including binding sites for OCT4, NANOG, SOX2, and SIN3A, paralleling embryonic stem cell biology...
January 10, 2019: Cell
Hsueh-Yao Chu, Long-Sheng Lu, Wanying Cho, Shin-Yao Wu, Yu-Cheng Chang, Chien-Ping Lin, Chih-Yung Yang, Chi-Hung Lin, Jeng-Kai Jiang, Fan-Gang Tseng
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers...
January 8, 2019: Cancers
Dan Wei, Xuejiao Zeng, Zhangru Yang, Quanyu Zhou, Xiaofu Weng, Hao He, Zhengqin Gu, Xunbin Wei
OBJECTIVE: Visualizing cell interactions in blood circulation is of great importance in studies of anticancer immunotherapy or drugs. However, the lack of a suitable imaging system hampers progress in this field. METHODS: In this work, we built a dual-channel in vivo imaging flow cytometer to visualize the interactions of circulating tumor cells (CTCs) and dendritic cells (DCs) simultaneously in the bloodstream. Two artificial neural networks were trained to identify blood vessels and cells in the acquired images...
January 7, 2019: IEEE Transactions on Bio-medical Engineering
Victor Navarro-Tableros, Yonathan Gomez, Giovanni Camussi, Maria Felice Brizzi
Lymphomas are heterogeneous diseases, and the term includes a number of histological subtypes that are characterized by different clinical behavior and molecular phenotypes. Valuable information on the presence of lymphoma cell-derived extracellular vesicles (LCEVs) in the bloodstream of patients suffering from this hematological cancer has recently been provided. In particular, it has been reported that the number and phenotype of LCEVs can both change as the disease progresses, as well as after treatment...
December 21, 2018: International Journal of Molecular Sciences
Xiping Yang, Yisheng Chen, Jianxin Li, Lijun Chen, Hefei Ren, Yang Liu, Xinyu Zhang
Traumatic brain injury (TBI) is the most common cause of death and permanent disability in people aged <45, and is associated with secondary brain injury and bleed progression, resulting in increased morbidity and mortality. TBI may also induce innate host defense responses characterized by activation of resident microglia and astrocytes, brain microvascular endothelial cells and peripheral blood monocytes. In the present study, 34 patients with moderate‑to‑severe traumatic brain injury were randomly divided into two groups, including a 7...
December 12, 2018: Molecular Medicine Reports
Arutha Kulasinghe, Joanna Kapeleris, Rebecca Kimberley, Stephen R Mattarollo, Erik W Thompson, Jean-Paul Thiery, Liz Kenny, Ken O'Byrne, Chamindie Punyadeera
Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD-L1) CTC chromosomal architecture (ALK, EGFR)...
November 22, 2018: Cancer Medicine
Yuhao Hu, Wanyi Tang, Pan Cheng, Quanyu Zhou, Xiaoying Tian, Xunbin Wei, Hao He
Circulating tumor cells (CTCs) play a key role in cancer metastasis but are very difficult to detect. in vivo monitoring CTCs has been recognized as an important technique for cancer research and clinical diagnosis. Recently, a noninvasive method, in vivo flow cytometry (IVFC) has been developed to enable continuous, real-time, and long-duration detection of CTCs in animal models by detecting CTC fluorescence in blood vessels excited by lasers. In this study, we present a simple optical scheme for direct noninvasive CTC detection using confocal microscopes...
December 17, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
H Skovierova, E Vidomanova, M Skoviera, B Tothova, E Halasova, J Strnadel
Metastasis development causes death in over 90% of cancer patients, and understanding the underlying biological features has long been hindered by difficulties in studying the widespread cancerous lesions and the absence of reliable methods of isolating and detecting viable metastatic cells during disease progression. These problems have an adverse impact on developing new agents capable of blocking cancer spread. Circulating tumor cells (CTCs) have a crucial role in carcinogenesis, and this review presents advanced understanding of the characteristics of CTCs and CTC cluster metastatic properties...
January 15, 2019: Neoplasma
Marcus Vetter, Julia Landin, Barbara Maria Szczerba, Francesc Castro-Giner, Sofia Gkountela, Cinzia Donato, Ilona Krol, Ramona Scherrer, Catharina Balmelli, Alexandra Malinovska, Alfred Zippelius, Christian Kurzeder, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Nicola Aceto
BACKGROUND: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive. METHODS: We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized by progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation...
November 20, 2018: Breast Cancer Research: BCR
Peter M Aldridge, Monorina Mukhopadhyay, Sharif U Ahmed, Wendi Zhou, Elisa Christinck, Rhema Makonnen, Edward H Sargent, Shana O Kelley
The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable noninvasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells-properties closely linked to their clinical behavior-demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into 10 discrete streams...
November 21, 2018: ACS Nano
Gerald Stübiger, Michael D Nairn, Tom K Abban, Matthew E Openshaw, Luis Mancera, Barbara Herzig, Michael Wuczkowski, Daniel Senfter, Robert M Mader
Cancer cells communicate with the whole organism via extracellular vesicles (EVs), which propagate molecular information in support of the malignant phenotype. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was employed for protein profiling of EVs derived from CCL-228 as the primary colon tumor, the lymph node metastasis CCL-227, and subclones resistant to 5, 25, and 125 μM 5-fluorouracil (FU). EVs were harvested from cell culture supernatant by ultracentrifugation to serve as a model for circulating cancer cell-derived biomarker carriers from body fluids (i...
November 1, 2018: Analytical Chemistry
Xia Liu, Rokana Taftaf, Madoka Kawaguchi, Ya-Fang Chang, Wenjing Chen, David Entenberg, Youbin Zhang, Lorenzo Gerratana, Simo Huang, Dhwani B Patel, Elizabeth Tsui, Valery Adorno-Cruz, Steven M Chirieleison, Yue Cao, Allison S Harney, Shivani Patel, Antonia Patsialou, Yang Shen, Stefanie Avril, Hannah L Gilmore, Justin D Lathia, Derek W Abbott, Massimo Cristofanilli, John S Condeelis, Huiping Liu
Circulating tumor cells (CTCs) seed cancer metastases; however, the underlying cellular and molecular mechanisms remain unclear. CTC clusters were less frequently detected but more metastatic than single CTCs of triple negative breast cancer patients and representative patient-derived-xenograft (PDX) models. Using intravital multiphoton microscopic imaging, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding...
October 25, 2018: Cancer Discovery
Angelika Terbuch, Jan B Adiprasito, Verena Stiegelbauer, Maximilian Seles, Christiane Klec, Georg P Pichler, Margit Resel, Florian Posch, Anna L Lembeck, Herbert Stöger, Joanna Szkandera, Karl Pummer, Thomas Bauernhofer, Georg C Hutterer, Armin Gerger, Michael Stotz, Martin Pichler
Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity...
October 12, 2018: International Journal of Molecular Sciences
Joel Pel, Wendy W Y Choi, Amy Leung, Gosuke Shibahara, Laura Gelinas, Milenko Despotovic, W Lloyd Ung, Andre Marziali
A challenge in the clinical adoption of cell-free DNA (cfDNA) liquid biopsies for cancer care is their high cost compared to potential reimbursement. The most common approach used in liquid biopsies to achieve high specificity detection of circulating tumor DNA (ctDNA) among a large background of normal cfDNA is to attach molecular barcodes to each DNA template, amplify it, and then sequence it many times to reach a low-error consensus. In applications where the highest possible specificity is required, error rate can be lowered further by independently detecting the sequences of both strands of the starting cfDNA...
2018: PloS One
Sotirios P Fortis, Christoforos K Vaxevanis, Louisa G Mahaira, Michael Sofopoulos, Nectaria N Sotiriadou, Amalia Dinou, Niki Arnogiannaki, Catherine Stavropoulos-Giokas, Dimitris Thanos, Constantin N Baxevanis, Sonia A Perez
Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy...
October 1, 2018: Cancer Immunology, Immunotherapy: CII
Tomoyuki Satake, Atsushi Suetsugu, Miki Nakamura, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
BACKGROUND/AIM: Circulating tumor cells (CTCs) may initiate metastasis. Some studies show that the number of CTCs and existence of CTC clusters can be prognostic. In the present study, our color-coded imaging nude mouse model of metastatic lymphoma was utilized to investigate the microenvironment of CTC clusters using fluorescent-protein imaging. MATERIALS AND METHODS: EL-4 mouse lymphoma cells expressing red fluorescent protein (RFP) were injected into the spleen of transgenic C57B/6-green fluorescent protein (GFP) mice...
October 2018: Anticancer Research
Sayon Basu, Sanith Cheriyamundath, Avri Ben-Ze'ev
Changes in cell adhesion and motility are considered key elements in determining the development of invasive and metastatic tumors. Co-opting the epithelial-to-mesenchymal transition (EMT) process, which is known to occur during embryonic development, and the associated changes in cell adhesion properties in cancer cells are considered major routes for tumor progression. More recent in vivo studies in tumor tissues and circulating tumor cell clusters suggest a stepwise EMT process rather than an "all-or-none" transition during tumor progression...
2018: F1000Research
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