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breast cancer, circulating tumor cells

Nick Beije, Wendy Onstenk, Jaco Kraan, Anieta M Sieuwerts, Paul Hamberg, Luc Y Dirix, Anja Brouwer, Felix E de Jongh, Agnes Jager, Caroline M Seynaeve, Ngoc M Van, John A Foekens, John W M Martens, Stefan Sleijfer
BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Jin Sun Lee, Mark Jesus M Magbanua, John W Park
Recent technological advancements in rare cell analysis have facilitated the detection of circulating tumor cells (CTCs) in the blood of patients diagnosed with breast and other types of cancers. Numerous clinical studies involving the enumeration of CTCs in breast cancer patients have unequivocally demonstrated the prognostic value of these cells. Evidence from recent molecular studies indicates that CTCs may be potential surrogate markers for systemic disease. As such, real-time assessment of therapeutic biomarkers in breast CTCs, such as the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), may have a tremendous impact in guiding-targeted cancer therapy...
October 19, 2016: Breast Cancer Research and Treatment
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection...
2016: PloS One
Svetlana N Tamkovich, Oleg S Tutanov, Danil S Serdukov, Maxim S Belenikin, Anatoliy G Shlikht, Natalia A Kirushina, Vladimir E Voytsitskiy, Yuri P Tsentalovich, Vsevolod A Tkachuk, Pavel P Laktionov
In the current study we have investigated the protein content of blood plasma deoxyribonucleoprotein complexes. The complexes were isolated using affinity chromatography with immobilized polyclonal anti-histone antibodies. Proteins were separated by SDS PAAGE and identified by MALDI-TOF mass-spectrometry. 111 and 56 proteins (excluding histones), respectively, were identified with a good score in deoxyribonucleoprotein complexes of healthy females and breast cancer patients. However, only four of these proteins were found in 30 % of all samples...
2016: Advances in Experimental Medicine and Biology
Manjima Dhar, Edward Pao, Corinne Renier, Derek E Go, James Che, Rosita Montoya, Rachel Conrad, Melissa Matsumoto, Kyra Heirich, Melanie Triboulet, Jianyu Rao, Stefanie S Jeffrey, Edward B Garon, Jonathan Goldman, Nagesh P Rao, Rajan Kulkarni, Elodie Sollier-Christen, Dino Di Carlo
Circulating tumor cells (CTCs) have a great potential as indicators of metastatic disease that may help physicians improve cancer prognostication, treatment and patient outcomes. Heterogeneous marker expression as well as the complexity of current antibody-based isolation and analysis systems highlights the need for alternative methods. In this work, we use a microfluidic Vortex device that can selectively isolate potential tumor cells from blood independent of cell surface expression. This system was adapted to interface with three protein-marker-free analysis techniques: (i) an in-flow automated image processing system to enumerate cells released, (ii) cytological analysis using Papanicolaou (Pap) staining and (iii) fluorescence in situ hybridization (FISH) targeting the ALK rearrangement...
October 14, 2016: Scientific Reports
Jonas Steenbrugge, Koen Breyne, Sofie Denies, Melissa Dekimpe, Kristel Demeyere, Olivier De Wever, Peter Vermeulen, Steven Van Laere, Niek N Sanders, Evelyne Meyer
Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice...
October 6, 2016: Journal of Mammary Gland Biology and Neoplasia
Shengnan Ma, Jie Zhou, Yuxin Zhang, Yiyan He, Qian Jiang, Dong Yue, Xianghui Xu, Zhongwei Gu
The stability dilemma and limited tumor penetration of nanocarriers in cancer chemotherapy remain two predominant challenges for their successful clinical translation. Herein, the pH-sensitive fluorocarbon functionalized nanocarriers (SFNs) with a tumor homing and penetrating peptide iRGD are reported to overcome the stability dilemma and enhance tumor accumulation and penetration in an orthotopic breast cancer. The highly stable SFNs with a low critical association concentration provide a safe and spacious harbor for hydrophobic drugs...
October 7, 2016: ACS Applied Materials & Interfaces
Zhaomei Mu, Naoual Benali-Furet, Georges Uzan, Anaëlle Znaty, Zhong Ye, Carmela Paolillo, Chun Wang, Laura Austin, Giovanna Rossi, Paolo Fortina, Hushan Yang, Massimo Cristofanilli
The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs...
September 30, 2016: International Journal of Molecular Sciences
Thomas M Deutsch, Sabine Riethdorf, Juliane Nees, Andreas D Hartkopf, Birgitt Schönfisch, Christoph Domschke, Martin R Sprick, Florian Schütz, Sara Y Brucker, Stefan Stefanovic, Christof Sohn, Klaus Pantel, Andreas Trumpp, Andreas Schneeweiss, Markus Wallwiener
PURPOSE: While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC...
November 2016: Breast Cancer Research and Treatment
Carmen Viski, Courtney König, Magdalena Kijewska, Carolin Mogler, Clare M Isacke, Hellmut G Augustin
Metastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts share a number of traits, including the upregulated expression of the transmembrane receptor endosialin (CD248). Comparative experiments in wild-type and endosialin-deficient mice revealed that stromal endosialin does not affect primary tumor growth but strongly promotes spontaneous metastasis...
September 15, 2016: Cancer Research
John D Hainsworth, Patrick B Murphy, Jose R Alemar, Brooke R Daniel, Robyn R Young, Denise A Yardley
PURPOSE: Determination of HER2 status by testing circulating tumor cells (CTCs), compared to sampling tumor biopsies, may improve patient management by allowing ongoing assessment of HER2 status during the disease course. The PRO Onc assay (Prometheus Laboratories; San Diego, CA) is a multiplexed immunoassay that measures the expression and activation of HER2 in CTCs. In this study, we screened patients with metastatic HER2-negative breast cancer with the PRO Onc assay; patients with HER2 overexpression or activation received a trial of HER2-targeted therapy...
November 2016: Breast Cancer Research and Treatment
Philip Hepp, Ulrich Andergassen, Bernadette Jäger, Elisabeth Trapp, Marianna Alunni-Fabbroni, Thomas W P Friedl, Nadeschda Hecker, Ralf Lorenz, Peter Fasching, Andreas Schneeweiss, Tanja Fehm, Wolfgang Janni, Brigitte Rack
BACKGROUND: Evidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up. PATIENTS AND METHODS: The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs...
September 2016: Anticancer Research
Tobias M Gorges, Andra Kuske, Katharina Röck, Oliver Mauermann, Volkmar Müller, Sven Peine, Karl Verpoort, Vendula Novosadova, Mikael Kubista, Sabine Riethdorf, Klaus Pantel
BACKGROUND: Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS: CTCs were enriched based on their EpCAM expression (CellSearch®) or by size and deformability (Parsortix™), identified by EpCAM and/or pan-keratin-specific antibodies, and isolated for single cell multiplex RNA profiling. RESULTS: Distinct breast and prostate CTC expression signatures could be discriminated from RNA profiles of leukocytes...
September 14, 2016: Clinical Chemistry
Huiping Sun, Jinghan Su, Qingshuo Meng, Qi Yin, Lingli Chen, Wangwen Gu, Pengcheng Zhang, Zhiwen Zhang, Haijun Yu, Siling Wang, Yaping Li
A unique biomimetic drug-delivery system composed of 4T1-breast-cancer-cell membranes and paclitaxel-loaded polymeric nanoparticles (PPNs) (cell-membrane-coated PPNs), demonstrates superior interactions to its source tumor cells and elongated blood circulation, and displays highly cell-specific targeting of the homotypic primary tumor and metastases, with successful inhibition of the growth and lung metastasis of the breast cancer cells.
September 15, 2016: Advanced Materials
Hyungseok Cho, Jinho Kim, Song-I Han, Ki-Ho Han
CTCs are currently in the spotlight because provide comprehensive genetic information that enables monitoring of the evolution of cancer and selection of appropriate therapeutic strategies that cannot be obtained from a single-site tumor biopsy. Despite their importance, current techniques for isolating CTCs are limited in terms of their ability to yield high-quality CTCs from peripheral blood for use in profiling cancer genetic mutations by DNA sequencing technologies. This paper introduces a lateral magnetophoretic microseparator (the 'CTC-μChip') for isolating highly pure CTCs from blood, which facilitates the detection of somatic mutations in isolated CTCs...
October 2016: Biomedical Microdevices
Sandra Casimiro, Arlindo R Ferreira, André Mansinho, Irina Alho, Luis Costa
Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors...
2016: International Journal of Molecular Sciences
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain...
2016: International Journal of Molecular Sciences
(no author information available yet)
Patients with ER(+)/HER2(-) breast cancer have interconverting HER2(+) and HER2(-) circulating tumor cells.
October 2016: Cancer Discovery
Ioana Laura Aanei, Adel M ElSohly, Michelle E Farkas, Chawita Netirojjanakul, Melanie Regan, Stephanie Taylor Murphy, James P O'Neil, Youngho Seo, Matthew B Francis
A variety of nanoscale scaffolds, including virus-like particles (VLPs), are being developed for biomedical applications; however, little information is available about their in vivo behavior. Targeted nanoparticles are particularly valuable as diagnostic and therapeutic carriers because they can increase the signal-to-background ratio of imaging agents, improve the efficacy of drugs, and reduce adverse effects by concentrating the therapeutic molecule in the region of interest. The genome-free capsid of bacteriophage MS2 has several features that make it well-suited for use in delivery applications, such as facile production and modification, the ability to display multiple copies of targeting ligands, and the capacity to deliver large payloads...
September 9, 2016: Molecular Pharmaceutics
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