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circulating tumor cell cluster

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
Veronica Huber, Viviana Vallacchi, Viktor Fleming, Xiaoying Hu, Agata Cova, Matteo Dugo, Eriomina Shahaj, Roberta Sulsenti, Elisabetta Vergani, Paola Filipazzi, Angela De Laurentiis, Luca Lalli, Lorenza Di Guardo, Roberto Patuzzo, Barbara Vergani, Elena Casiraghi, Mara Cossa, Ambra Gualeni, Valentina Bollati, Flavio Arienti, Filippo De Braud, Luigi Mariani, Antonello Villa, Peter Altevogt, Viktor Umansky, Monica Rodolfo, Licia Rivoltini
The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and with resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection...
September 27, 2018: Journal of Clinical Investigation
Shira Ronen, Steven H Kroft, Horatiu Olteanu, Paul R Hosking, Alexandra M Harrington
INTRODUCTION: Carcinocythemia is a rare phenomenon defined as morphologically identifiable, circulating tumor cells in the peripheral blood. No modern case series of carcinocythemia exists in the literature. METHODS: Blood smears from carcinocythemia patients were reviewed and associated clinicopathologic findings described and compared to the literature. When available, bone marrows were examined. RESULTS: We identified 7 carcinocythemia cases over 3 years at our institution in 5 females and 2 males with a median age of 57 and compare them to 26 case reports in the literature (19 females, 10 males; median age 57)...
September 14, 2018: International Journal of Laboratory Hematology
Anna P Sokolenko, Evgeny N Imyanitov
There are multiple applications of molecular tests in clinical oncology. Mutation analysis is now routinely utilized for the diagnosis of hereditary cancer syndromes. Healthy carriers of cancer-predisposing mutations benefit from tight medical surveillance and various preventive interventions. Cancers caused by germ-line mutations often require significant modification of the treatment strategy. Personalized selection of cancer drugs based on the presence of actionable mutations has become an integral part of cancer therapy...
2018: Frontiers in Molecular Biosciences
Constantin Nelep, Jens Eberhardt
Molecular analysis of rare single cells like circulating tumor cells (CTCs) from whole blood patient samples bears multiple challenges. One of those challenges is the efficient and ideally loss-free isolation of CTCs over contaminating white and red blood cells. While there is a multitude of commercial and non-commercial systems available for the enrichment of CTCs their cell output does not deliver the purity most molecular analysis methods require. Here we describe the ALS CellCelector™ which can solve this challenge allowing the retrieval of 100% pure single CTCs from blood processed by different upstream enrichment techniques...
September 5, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Xinying Meng, Xinjuan Yu, Quanjiang Dong, Xiaona Xu, Jinghua Li, Qianqian Xu, Jian Ma, Changhong Zhou
Circulating follicular helper T (cTfh) cells are a novel subset of cluster of differentiation (CD)4+ helper T cells. Interleukin (IL)-21 and C-X-C motif chemokine ligand (CXCL)13 are the principal effectors and chemotactic regulatory factors of Tfh. However, the roles of IL-21 and CXCL13 in gastric cancer have not yet been completely elucidated. The aim of the present study was to investigate the distribution of cTfh cells, and the expression of IL-21 and CXCL13 in patients with gastric cancer was evaluated in order to ascertain the significance and potential mechanisms of these effectors in gastric cancer...
September 2018: Oncology Letters
Dandan Xue, Tiansong Xia, Jue Wang, Meihong Chong, Shui Wang, Chunhui Zhang
Circulating tumor cells (CTCs) dissemination is involved in tumor metastasis and is an independent prognostic factor in patients with primary and metastatic breast cancer. Regulatory T cells (Tregs) and cluster of differentiation (CD)8+ T lymphocytes are the main types of immune cells in the tumor microenvironment and exert opposite roles on the progression and outcome of breast cancer. The aim of the present study was to evaluate the associations between CTCs and intratumoral/peritumoral Tregs and CD8+ T lymphocytes in breast cancer...
September 2018: Oncology Letters
Yi Hu, Weibo Qi, Li Sun, Hui Zhou, Biliu Zhou, Zhiping Yang
Metastatic circulating tumor cells in non-small cell lung cancer (NSCLC) metastasis have been reported to be associated with an immune response. The present study aimed to provide a theoretical basis for the immunomodulatory processes during NSCLC blood metastasis. NSCLC blood and normal peripheral blood mononuclear cells (PBMCs) were collected. The quantity of cluster of differentiation (CD)4+ CD25high regulatory T (Treg) cells and the intracellular forkhead box protein 3 (Foxp3) expression in CD4+ CD25high Treg cells were determined by flow cytometry...
August 2018: Experimental and Therapeutic Medicine
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...
September 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. Reviews on cancer
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...
August 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
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