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circulating tumor cell cluster

Georgios Gemenetzis, Vincent P Groot, Jun Yu, Ding Ding, Jonathan A Teinor, Ammar A Javed, Laura D Wood, Richard A Burkhart, John L Cameron, Martin A Makary, Matthew J Weiss, Jin He, Christopher L Wolfgang
OBJECTIVES: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes correlate with overall survival in patients with pancreatic ductal adenocarcinoma (PDAC). Herein, we report results of a prospective observational study on CTCs dynamics to assess their clinical significance. METHODS: The CLUSTER study is a prospective longitudinal study on PDAC CTCs dynamics (NCT02974764). Multiple peripheral blood samples were collected from 200 consecutively enrolled patients with presumed PDAC diagnosis...
August 3, 2018: Annals of Surgery
J Pablo Arnoletti, Na'im Fanaian, Joseph Reza, Ryan Sause, Alvin Jo Almodovar, Milan Srivastava, Swati Patel, Paula P Veldhuis, Elizabeth Griffith, Yai-Ping Shao, Xiang Zhu, Sally A Litherland
Circulating tumor cells (CTC) enter the blood from many carcinomas and represent a likely source of metastatic dissemination. In contrast to the peripheral circulation, KRAS mutation- positive CTC thrive in the portal venous blood of patients with pancreatic ductal adenocarcinoma (PDAC). To analyze the essential interactions that contribute to carcinoma CTC growth and immune resistance, portal venous blood was collected during pancreatico-duodenectomy in 41 patients with peri-ampullary pathologies (PDAC = 11; ampullary adenocarcinoma (AA) = 15; distal cholangiocarcinoma (CC) = 6; IPMN = 7; non-malignant pancreatitis = 2)...
August 1, 2018: Cancer Biology & Therapy
Andreas Josefsson, Karin Larsson, Marianne Månsson, Jens Björkman, Eva Rohlova, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén
Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients...
June 29, 2018: Oncotarget
Shubham Tripathi, Mohit Kumar Jolly, Wendy A Woodward, Herbert Levine, Michael W Deem
Clusters of circulating tumor cells (CTCs), despite being rare, may account for more than 90% of metastases. Cells in these clusters do not undergo a complete epithelial-to-mesenchymal transition (EMT), but retain some epithelial traits as compared to individually disseminating tumor cells. Determinants of single cell dissemination versus collective dissemination remain elusive. Inflammatory breast cancer (IBC), a highly aggressive breast cancer subtype that chiefly metastasizes via CTC clusters, is a promising model for studying mechanisms of collective tumor cell dissemination...
2018: Frontiers in Oncology
Mohit Kumar Jolly, Sendurai A Mani, Herbert Levine
Metastasis is the leading cause of mortality among cancer patients. Dissemination enabled by an epithelial-to-mesenchymal transition (EMT) of carcinoma cells has long been considered to be the predominant mechanism for carcinoma metastasis, based on overexpression studies of many EMT-inducing transcription factors. Individual CTCs - and a binary framework of EMT - have been long considered to be sufficient and necessary condition for metastasis. However, recent studies have shown that collective migration and invasion through tumor buds and clusters of Circulating Tumor Cells (CTCs) as possibly being the prevalent mode of metastasis, although individual CTCs may still contribute to metastasis...
July 8, 2018: Biochimica et Biophysica Acta
G Kallergi, D Aggouraki, N Zacharopoulou, C Stournaras, V Georgoulias, S S Martin
BACKGROUND: Circulating tumor cells (CTCs) are the major players in the metastatic process. A potential mechanism of cell migration and invasion is the formation of microtentacles in tumor cells. These structures are supported by α-tubulin (TUB), detyrosinated α-tubulin (GLU), and vimentin (VIM). In the current study, we evaluated the expression of those cytoskeletal proteins in CTCs. METHODS: Forty patients with breast cancer (BC) (16 early and 24 metastatic) were enrolled in the study...
July 5, 2018: Breast Cancer Research: BCR
Mengxi Wu, Po-Hsun Huang, Rui Zhang, Zhangming Mao, Chuyi Chen, Gabor Kemeny, Peng Li, Adrian V Lee, Rekha Gyanchandani, Andrew J Armstrong, Ming Dao, Subra Suresh, Tony Jun Huang
The study of circulating tumor cells (CTCs) offers pathways to develop new diagnostic and prognostic biomarkers that benefit cancer treatments. In order to fully exploit and interpret the information provided by CTCs, the development of a platform is reported that integrates acoustics and microfluidics to isolate rare CTCs from peripheral blood in high throughput while preserving their structural, biological, and functional integrity. Cancer cells are first isolated from leukocytes with a throughput of 7.5 mL h-1 , achieving a recovery rate of at least 86% while maintaining the cells' ability to proliferate...
July 3, 2018: Small
Bruno Martinucci, Brenda de Carvalho Minatel, Maira Smaniotto Cucielo, Mariana Medeiros, Ivan José Vechetti-Junior, Sérgio Luis Felisbino, Flávia Karina Delella
Prostate cancer (PCa) has high mortality rates, with most of the deaths resulting from the development of metastasis. Fibronectin (FN) plays key roles in cell adhesion and affects the migratory behavior of cells. In the tumor microenvironment and also in the blood plasma during metastasis, FN displays increased expression, however its role in prostate cancer remains poorly understood. This study aimed to unveil the specific roles of FN as a soluble component, alone or in combination with a complex basement membrane...
June 30, 2018: Molecular and Cellular Biochemistry
Michelle B Chen, Cynthia Hajal, David C Benjamin, Cathy Yu, Hesham Azizgolshani, Richard O Hynes, Roger D Kamm
Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell-cell interactions...
July 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
James B McCarthy, Dorraya El-Ashry, Eva A Turley
This review summarizes the roles of CAFs in forming a "cancerized" fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA) in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM) and associated biomechanical changes in tumor stroma...
2018: Frontiers in Cell and Developmental Biology
Liangliang Wu, Hongyu Liu, Hongchuan Guo, Qiong Wu, Songyan Yu, Yuanyuan Qin, Gang Wang, Qiyan Wu, Rong Zhang, Lingxiong Wang, Lijun Zhang, Chunxi Liu, Shunchang Jiao, Tianyi Liu
Myeloid-derived suppressor cells (MDSCs) serve an immunosuppressive role in human tumors. Human Lin-/low human leukocyte antigen-antigen D related (HLA-DR- ) cluster of differentiation (CD)-11b+ CD33+ MDSCs are closely linked with tumor staging, progression, clinical therapeutic efficacy and prognosis for various types of tumors. The present study employed multiparametric flow cytometry to measure the proportion of Lin-/low HLA-DR- CD11b+ CD33+ MDSCs in the peripheral blood of 105 cervical cancer patients and 50 healthy subjects...
June 2018: Oncology Letters
Mohamed El-Mogy, Bernard Lam, Taha A Haj-Ahmad, Shannon McGowan, Darrick Yu, Lucas Nosal, Nezar Rghei, Pam Roberts, Yousef Haj-Ahmad
BACKGROUND: Small RNAs are critical components in regulating various cellular pathways. These molecules may be tissue-associated or circulating in bodily fluids and have been shown to associate with different tumors. Next generation sequencing (NGS) on small RNAs is a powerful tool for profiling and discovery of microRNAs (miRNAs). RESULTS: In this study, we isolated total RNA from various bodily fluids: blood, leukocytes, serum, plasma, saliva, cell-free saliva, urine and cell-free urine...
May 29, 2018: BMC Genomics
Wanlei Gao, Ting Huang, Haojun Yuan, Jun Yang, Qinghui Jin, Chunping Jia, Guoxin Mao, Jianlong Zhao
Circulating tumor cells (CTCs) have become an important biomarker for liquid biopsy to monitor tumor progression and indicate response to therapies. Many epithelial cellular adhesion molecule (EpCAM) dependent CTC isolation methods have been developed, which have a limitation for low EpCAM expressed tumor cells. In an effort to overcome these drawbacks, we developed combined immunomagnetic beads (EpCAM, Mucin1 and epidermal growth factor receptor) to sensitively isolate CTCs for immunofluorescence analysis and genetic characterization...
August 1, 2018: Talanta
Muhammad Umer, Ramanathan Vaidyanathan, Nam-Trung Nguyen, Muhammad J A Shiddiky
Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts...
July 2018: Biotechnology Advances
Chiara Verdelli, Irene Forno, Annamaria Morotti, Pasquale Creo, Vito Guarnieri, Alfredo Scillitani, Filomena Cetani, Leonardo Vicentini, Gianni Balza, Edoardo Beretta, Stefano Ferrero, Valentina Vaira, Sabrina Corbetta
Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas ( n  = 15). Through in situ hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets CDKN1A /p21 and LATS2 at both mRNA and protein levels...
July 2018: Endocrine-related Cancer
Francesco Marchesi, Giulia Regazzo, Francesca Palombi, Irene Terrenato, Andrea Sacconi, Manuela Spagnuolo, Sara Donzelli, Mirella Marino, Cristiana Ercolani, Anna Di Benedetto, Giovanni Blandino, Gennaro Ciliberto, Andrea Mengarelli, Maria Giulia Rizzo
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line treatment. MicroRNAs (miRNAs) are under investigation as novel diagnostic and prognostic biomarkers in several malignancies, including malignant lymphomas. While tissue miRNAs in DLBCL patients have been extensively studied as biomarkers, only few reports to date have evaluated the role of circulating/serum miRNAs as potential prognostic factors...
May 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
Chiara Nicolazzo, Luciano Colangelo, Alessandro Corsi, Guido Carpino, Angela Gradilone, Chiara Sonato, Cristina Raimondi, Eugenio Gaudio, Paola Gazzaniga, Walter Gianni
Hemangiopericytoma (HPT) is a rare mesenchymal tumor of fibroblastic type and for its rarity is poorly studied. The most common sites of metastatic disease in patients with intracranial HPT are the bone, liver, and lung, suggestive for an hematogenous dissemination; for this reason, we investigated, for the first time, the presence of circulating tumor cells (CTCs) in hemangiopericytoma patient by CellSearch® and SceenCell® devices. Peripheral blood samples were drawn and processed by CellSearch, an EpCAM-dependent device, and ScreenCell®, a device size based...
2018: Analytical Cellular Pathology (Amsterdam)
María Gallardo-Gómez, Sebastian Moran, María Páez de la Cadena, Vicenta Soledad Martínez-Zorzano, Francisco Javier Rodríguez-Berrocal, Mar Rodríguez-Girondo, Manel Esteller, Joaquín Cubiella, Luis Bujanda, Antoni Castells, Francesc Balaguer, Rodrigo Jover, Loretta De Chiara
Background: Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers...
2018: Clinical Epigenetics
Alexander N May, Bryan D Crawford, Aurora M Nedelcu
The isolation of clusters of circulating tumor cells (CTCs) from cancer patients has recently challenged the accepted view that the initiation of secondary tumors during metastasis involves the dissemination of individual cancer cells. As such clusters appear to be more aggressive than single tumor cells, CTC clusters are now considered a main player in the metastatic process, and many studies are exploring their diagnostic, prognostic, and clinical significance. However, several technical challenges limit advances in this area...
2018: Frontiers in Oncology
Soroush Samadian, Jeff P Bruce, Trevor J Pugh
Somatic copy number variations (CNVs) play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequence data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introduce user-defined haplotype-phased allele-specific copy number events into an existing Binary Alignment Mapping (BAM) file, with a focus on targeted and exome sequencing experiments...
March 2018: PLoS Computational Biology
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