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breast cancer, circulating tumor cells

W Goto, S Kashiwagi, Y Asano, K Takada, K Takahashi, T Hatano, T Takashima, S Tomita, H Motomura, M Ohsawa, K Hirakawa, M Ohira
[This corrects the article DOI: 10.1186/s40364-017-0099-2.].
2018: Biomarker Research
Aynur Abdulla, Wenjia Liu, Azarmidokht Gholamipour-Shirazi, Jiahui Sun, Xianting Ding
Circulating tumor cells (CTCs) are rare cells that detach from primary or metastasis tumor and flow into the blood stream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literatures demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force...
March 14, 2018: Analytical Chemistry
Laura Lupini, Anna Moretti, Cristian Bassi, Alessio Schirone, Massimo Pedriali, Patrizia Querzoli, Roberta Roncarati, Antonio Frassoldati, Massimo Negrini
Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0...
March 12, 2018: Scientific Reports
Chunhui Ruan, Lisha Liu, Qingbing Wang, Xinli Chen, Qinjun Chen, Yifei Lu, Yu Zhang, Xi He, Yujie Zhang, Qin Guo, Tao Sun, Chen Jiang
An ideal gene-carrying vector is supposed to exhibit outstanding gene condensing capability with positively charged macromolecules to protect the carried gene during in vivo circulation, and a rapid dissociation upon microenvironmental stimuli at the aimed sites to release the escorted gene. Currently, it still remains a challenge to develop an ideal gene carrier with efficient transfection ability and meanwhile low toxicity for clinical applications. Herein, we innovatively introduced a ROS-biodegradable boric acid ester linkage in elaborating the design of gene carrier...
March 2, 2018: ACS Applied Materials & Interfaces
Fabienne Schochter, Brigitte Rack, Marie Tzschaschel, Arkadius Polasik, Ulrich Andergassen, Elisabeth Trapp, Marianna Alunni-Fabbroni, Andreas Schneeweiss, Volkmar Müller, Klaus Pantel, Jörg Gade, Ralf Lorenz, Mahdi Rezai, Hans Tesch, Ulrike Soeling, Tanja Fehm, Sven Mahner, Christian Schindlbeck, Werner Lichtenegger, Matthias W Beckmann, Peter A Fasching, Wolfgang Janni, Thomas W P Friedl
BACKGROUND: Optimal choice and sequence of endocrine treatment following adjuvant chemotherapy in postmenopausal early breast cancer patients are still under discussion and treatment stratification factors are missing. PATIENTS AND METHODS: Postmenopausal women with HER2-negative, hormone receptor-positive tumors and persisting circulating tumor cells (CTCs; assessed using the FDA-approved CellSearch® System, Janssen Diagnostics, LLC) after chemotherapy were randomized to 2 years of tamoxifen followed by 3 years of exemestane (tamoxifen-exemestane group, n = 54) or 5 years of exemestane (exemestane-only group, n = 54)...
2018: Oncology Research and Treatment
Fabien Gava, Lise Rigal, Odile Mondesert, Elise Pesce, Bernard Ducommun, Valérie Lobjois
BACKGROUND: Cancer cell aggregation is a key process involved in the formation of clusters of circulating tumor cells. We previously reported that cell-cell adhesion proteins, such as E-cadherin, and desmosomal proteins are involved in cell aggregation to form clusters independently of cell migration or matrix adhesion. Here, we investigated the involvement of gap junction intercellular communication (GJIC) during anchorage-independent clustering of MCF7 breast adenocarcinoma cells. METHODS: We used live cell image acquisition and analysis to monitor the kinetics of MCF7 cell clustering in the presence/absence of GJIC pharmacological inhibitors and to screen a LOPAC® bioactive compound library...
February 27, 2018: BMC Cancer
Ahmed F Salem, Si Wang, Sandrine Billet, Jie-Fu Chen, Parima Udompholkul, Luca Gambini, Carlo Baggio, Hsian-Rong Tseng, Edwin M Posadas, Neil A Bhowmick, Maurizio Pellecchia
EphA2 overexpression has been associated with metastasis in multiple cancer types, including melanomas and ovarian, prostate, lung, and breast cancers. We have recently proposed the development of peptide-drug conjugates (PDCs) using agonistic EphA2-targeting agents, such as the YSA peptide or its optimized version, 123B9. Although our studies indicated that YSA- and 123B9-drug conjugates can selectively deliver cytotoxic drugs to cancer cells in vivo, the relatively low cellular agonistic activities (i.e., the high micromolar concentrations required) of the agents toward the EphA2 receptor remained a limiting factor to the further development of these PDCs in the clinic...
February 27, 2018: Journal of Medicinal Chemistry
Tania B Porras, Pushpinder Kaur, Alexander Ring, Naomi Schechter, Julie E Lang
Circulating tumor cells (CTCs) have potential utility as a surrogate biomarker of tumor biology via a liquid biopsy. The aim of this study was to evaluate if the nCounter NanoString assay could be used for accurate gene expression profiling of CTCs using the PAM50 research-use-only CodeSet. Analysis was performed on CTCs isolated by the ANGLE Parsortix system from healthy blood spiked with the breast cancer cell lines Hs578T, SkBr3, MDA-MB-231 or MCF7. Using cell lines as gold standard positive controls and Parsortix processed blood without spiking (unspiked) as negative controls, we found an average of 12 significantly differentially expressed genes among spiked samples versus unspiked controls...
January 23, 2018: Oncotarget
Teruo Yamauchi, Jose Rodrigo Espinosa Fernandez, Chiyo K Imamura, Hideko Yamauchi, Hiromitsu Jinno, Maiko Takahashi, Yuko Kitagawa, Seigo Nakamura, Bora Lim, Savitri Krishnamurthy, James M Reuben, Diane Liu, Debasish Tripathy, Helen Chen, Naoko Takebe, Hideyuki Saya, Naoto T Ueno
Chemotherapy has been reported to increase the proportion of cancer stem cells (CSCs) and to promote epithelial-mesenchymal transition (EMT) phenotype changes. Anti-HER2 therapy may provide a strategy for eliminating CSC and EMT, which contribute to therapeutic resistance. No study has determined the changes in the quantity or characteristics of CSCs or circulating tumor cells (CTCs) with EMT phenotype during preoperative anti-HER2 therapy, and whether these changes correlate to response to dual anti-HER2 therapy...
January 23, 2018: Oncotarget
Hanna Huebner, Peter A Fasching, Walter Gumbrecht, Sebastian Jud, Claudia Rauh, Mark Matzas, Peter Paulicka, Katja Friedrich, Michael P Lux, Bernhard Volz, Paul Gass, Lothar Häberle, Franziska Meier-Stiegen, Andreas Hartkopf, Hans Neubauer, Katrin Almstedt, Matthias W Beckmann, Tanja N Fehm, Matthias Ruebner
BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform. METHODS: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform...
February 20, 2018: BMC Cancer
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
Boxuan Ma, Weihua Zhuang, Yanan Wang, Rifang Luo, Yunbing Wang
Intelligent drug delivery systems with prolonged circulation time, reduced drug leakage in blood, target site-triggered drug release and endosomal escape are attractive and ideal for malignant tumor therapy. Herein, doxorubicin (DOX)-conjugated smart polymeric micelles based on 4-carboxy benzaldehyde-grafted poly (L-lysine)-block-poly (methacryloyloxyethyl phosphorylcholine) (PLL(CB/DOX)-b-PMPC) copolymer are prepared. DOX and electronegative 4-carboxy benzaldehyde are conjugated to the PLL block via an imine linkage and as a result, the drug loaded micelles exhibited the pH-triggered charge-conversion property and accelerated drug release at tumor pH...
February 13, 2018: Acta Biomaterialia
Ivana Bratić Hench, Jürgen Hench, Markus Tolnay
Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as "liquid biopsies," are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities...
2018: Frontiers in Medicine
Ka-Wai Tam, Chi-Tang Ho, Shih-Hsin Tu, Wen-Jui Lee, Ching-Shui Huang, Ching-Shyang Chen, Chih-Hsiung Wu, Chia-Hwa Lee, Yuan-Soon Ho
Vitamin E (Vit. E) is considered an essential dietary nutrient for humans and animals. An enormous body of evidence indicates the biological and protective effects of Vit. E consumption. Tocopherol-associated protein (TAP) is a major tocopherol-binding protein affecting Vit. E stimulation and downstream signaling transduction. However, how Vit. E utilizes TAP as an anti-cancer mechanism remains unclear. Microarray analysis of signature gene profiles in breast cancer cells treated with α-tocopheryl succinate (α-TOS, a Vit...
January 12, 2018: Oncotarget
Lu Xu, Songlin Jia, Hengyu Li, Yue Yu, Guoping Liu, Yanmei Wu, Xishui Liu, Chaoqian Liu, Yue Zhou, Zhenzhen Zhang, Yuan Sheng
Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90...
February 2018: Oncology Letters
Jonathan R McDaniel, Stephanie C Pero, William N Voss, Girja S Shukla, Yujing Sun, Sebastian Schaetzle, Chang-Han Lee, Andrew P Horton, Seth Harlow, Jimmy Gollihar, Jared W Ellefson, Christopher C Krag, Yuri Tanno, Nikoletta Sidiropoulos, George Georgiou, Gregory C Ippolito, David N Krag
A better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood...
February 9, 2018: Cancer Immunology, Immunotherapy: CII
Weikai Zhang, Zhitao Li, Zihua Wang, Chunyan Yue, Hui Zheng, Ren Li, Mingxing Zhou, Zhiyuan Hu, Zewen Wei, Qin Li
Here, we provide direct evidence that using recombinant proteins expressed in eukaryotic cells as antigen is a practical way to generate monoclonal antibodies (mAbs) against heavily glycosylated proteins. Heavily glycosylated proteins are typically difficult targets for mAb generation, being limited by unsatisfactory affinity and low specificity. Using the heavily glycosylated CD45 protein as an example, we demonstrate the entire process of expressing the protein in eukaryotic cells and using it as an antigen to generate CD45-targeting mAbs in mice...
2018: PloS One
Eric M Bressler, Jayoung Kim, Ron B Shmueli, Adam C Mirando, Hojjat Bazzazi, Esak Lee, Aleksander S Popel, Niranjan B Pandey, Jordan J Green
While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show non-specific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue...
February 9, 2018: Journal of Biomedical Materials Research. Part A
Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka
Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls of 28 healthy women...
January 9, 2018: Oncotarget
Rong-Rui Wei, Dan-Ni Sun, Hong Yang, Juan Yan, Xiong Zhang, Xing-Ling Zheng, Xu-Hong Fu, Mei-Yu Geng, Xun Huang, Jian Ding
Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE)...
February 8, 2018: Acta Pharmacologica Sinica
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