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Circulating tumor cell

Jelena Belic, Marina Koch, Peter Ulz, Martina Auer, Teresa Gerhalter, Sumitra Mohan, Katja Fischereder, Edgar Petru, Thomas Bauernhofer, Jochen B Geigl, Michael R Speicher, Ellen Heitzer
Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. Comprehensive genome-wide analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. In order to develop a fast and cost-effective pre-screening method for the identification of plasma samples suitable for further extensive qualitative analysis, we adapted the recently described FAST-SeqS method...
2016: Advances in Experimental Medicine and Biology
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
Erina Takai, Yasushi Totoki, Hiromi Nakamura, Mamoru Kato, Tatsuhiro Shibata, Shinichi Yachida
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect molecular characteristics of tumors, supporting the concept of "liquid biopsy".We determined the mutational status of KRAS in plasma cfDNA using multiplex droplet digital PCR in 259 patients with PDAC, retrospectively...
2016: Advances in Experimental Medicine and Biology
Xiaodan Meng, Volkmar Müller, Karin Milde-Langosch, Fabian Trillsch, Klaus Pantel, Heidi Schwarzenbach
In the present study, we investigated whether circulating cell-free microRNAs serve as potential biomarkers in epithelial ovarian cancer (EOC) patients. Circulating miR-373, miR-200a, miR-200b and miR-200c were quantified in a cohort of 60 EOC patients, 20 patients with benign ovarian diseases and 32 healthy women using quantitative TaqMan MicroRNA assays. The serum concentrations of cell-free miR-373, miR-200a, miR-200b and miR-200c were significantly higher in EOC patients than in healthy women (p = 0.0001)...
2016: Advances in Experimental Medicine and Biology
Kelly Aubertin, Amanda K A Silva, Nathalie Luciani, Ana Espinosa, Aurélie Djemat, Dominique Charue, François Gallet, Olivier Blanc-Brude, Claire Wilhelm
Photodynamic therapy is an emerging cancer treatment that is particularly adapted for localized malignant tumor. The phototherapeutic agent is generally injected in the bloodstream and circulates in the whole organism as a chemotherapeutic agent, but needs light triggering to induce localized therapeutic effects. We found that one of the responses of in vitro and in vivo cancer cells to photodynamic therapy was a massive production and emission of extracellular vesicles (EVs): only 1 hour after the photo-activation, thousands of vesicles per cell were emitted in the extracellular medium...
October 18, 2016: Scientific Reports
Philip H Abbosh, Jonathan E Rosenberg, Elizabeth R Plimack
There are very few biomarkers used to diagnose bladder cancer and no clinically approved biomarkers for prediction or prognostication of this disease. All currently available biomarkers are based on urine tests, and thus, they may not be applicable to patients with extravesical tumors. Biopsy of metastatic sites requires an invasive procedure, whereas serum-based markers, which can be easily obtained and serially measured, thus have obvious merit. These deficiencies may be overcome with advances in genome sequencing, identification of circulating tumor cells, and RNA-, protein-, and DNA-based biomarkers...
October 14, 2016: Urologic Oncology
Angela W Dymond, Colin Howes, Christine Pattison, Karen So, Gabriella Mariani, Mark Savage, Stuart Mair, Gill Ford, Paul Martin
PURPOSE: Selumetinib (AZD6244, ARRY-142886), an oral mitogen activated kinase 1/2 inhibitor, is in clinical development for the treatment of a variety of different tumor types. Herein, we report a study that determined the distribution, metabolism, and excretion of selumetinib in healthy male volunteers. METHODS: In this open-label, single-center, Phase I clinical trial, 6 subjects received a single 75-mg dose of [(14)C]-selumetinib. Blood and excreta samples were collected for pharmacokinetic and radiometric analyses...
October 14, 2016: Clinical Therapeutics
Ji-Youn Han, Jae-Jin Choi, Jin Young Kim, You Lim Han, Geon Kook Lee
No abstract text is available yet for this article.
October 17, 2016: BMC Cancer
Qing Zhang, Haoyu Zhao, Dong Li, Liping Liu, Shuhu Du
To achieve drug targeting and on-demand releasing, surface functionalization plays a critical role in fabricating potential mesoporous silica nanoparticles (MSNs) toward tumor chemotherapy. Here, we prepared a size-controllable ligand-functionalized MSNs delivery system via coordinate bonding, which can release doxorubicin (DOX) in response to pH and prolong the circulation time of drug in vivo. After modifying the external surface of MSNs with polyethylene glycol (PEG), iminodiacetic acid (IDA) as a ligand was mainly grafted on the surface of mesopores to chelate cupric iron and DOX in sequence via coordinate bonds...
October 11, 2016: Colloids and Surfaces. B, Biointerfaces
Daniel H Hovelson, Scott A Tomlins
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC...
September 2016: Cancer Journal
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
Jason Zhu, John H Strickler
"Liquid biopsies" are blood based assays used to detect and analyze circulating tumor products, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating microRNA (miRNA), circulating exosomes, and tumor educated platelets (TEP). For patients with gastrointestinal (GI) malignancies, blood based biopsies may offer several advantages. First, tumor tissue samples are often challenging to procure, and when obtainable, are often insufficient for genomic profiling...
October 2016: Journal of Gastrointestinal Oncology
Luciana De Luca, Giovanni D'Arena, Vittorio Simeon, Stefania Trino, Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Oreste Villani, Giovanna Mansueto, Silvia Deaglio, Idanna Innocenti, Luca Laurenti, Stefano Molica, Giuseppe Pietrantuono, Angelo De Stradis, Luigi Del Vecchio, Pellegrino Musto
Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease...
October 14, 2016: Leukemia & Lymphoma
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
Shweta Sharma, Ashwni Kumar Verma, Jyotsana Singh, B Venkatesh Teja, Naresh Mittapelly, Gitu Pandey, Sandeep Urandur, Ravi Shukla, Rituraj Konwar, Prabhat Ranjan Mishra
This study reports the development of Vitamin B6 (VitB6) modified pH sensitive charge reversal nanoparticles for efficient intracellular delivery of Doxorubicin (DOX). Herein, VitB6 was conjugated to stearic acid and the nanoparticles of the lipid were formulated by solvent injection method (DOX-B6-SA-NP). Due to the pKa (5.6) of VitB6, DOX-B6-SA-NP showed positive charge and enhanced release of DOX at pH 5. Confocal microscopy illustrated that DOX-B6-SA-NP treatment keep higher DOX accumulation inside the cells that conventional pH insensitive lipid nanoparticles (DOX-SA-NP)...
October 14, 2016: ACS Applied Materials & Interfaces
Katarzyna A Rejniak
Solid tumor dissemination from the primary site to the sites of metastasis involves tumor cell transport through the blood or lymph circulation systems. Once the tumor cells enter the bloodstream, they encounter a new hostile microenvironment. The cells must withstand hemodynamic forces and overcome the effects of fluid shear. The cells are exposed to immunological signaling insults from leukocytes, to collisions with erythrocytes, and to interactions with platelets or macrophages. Finally, the cells need to attach to the blood vessel walls and extravasate to the surrounding stroma to form tumor metastases...
2016: Advances in Experimental Medicine and Biology
L L Xiao, Y Liu, S Chen, B M Fu
Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cell (RBC) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation...
October 13, 2016: Biomechanics and Modeling in Mechanobiology
Wanjun Zhu, Xiao-Yan Zhang, Sadie L Marjani, Jialing Zhang, Wengeng Zhang, Shixiu Wu, Xinghua Pan
Single-cell sequencing (SCS) is a fast-growing, exciting field in genomic medicine. It enables the high-resolution study of cellular heterogeneity, and reveals the molecular basis of complicated systems, which facilitates the identification of new biomarkers for diagnosis and for targeting therapies. It also directly promotes the next generation of genomic medicine because of its ultra-high resolution and sensitivity that allows for the non-invasive and early detection of abnormalities, such as aneuploidy, chromosomal translocation, and single-gene disorders...
October 13, 2016: Cellular and Molecular Life Sciences: CMLS
Qiang Ding, Yujia Xia, Shuping Ding, Panpan Lu, Liang Sun, Yuhui Fan, Xin Li, Ying Wang, De-An Tian, Mei Liu
Transendothelial migration is a pivotal step before the dissemination of tumor cells into the blood circulation. Related researches about the crosstalk between tumor cells and endothelial cells could contribute to understanding the mechanism of transendothelial migration. Cumulative studies showed that CD133 was an important marker for cancer stem cells. In our research, a co-culture system was developed to study the interaction between CD133+ liver cancer cells and human umbilical vein endothelial cells. The results showed that the direct co-cultured supernatants promoted the migration and invasion of CD133+ liver cancer cells...
July 2016: Genes & Cancer
Margherita Correnti, Chiara Raggi
Poor prognosis and high recurrence remain leading causes of primary liver cancer-associated mortality. The spread of circulating tumor cells (CTCs) in the blood plays a major role in the initiation of metastasis and tumor recurrence after surgery. Nevertheless, only a subset of CTCs can survive, migrate to distant sites and establish secondary tumors. Consistent with cancer stem cell (CSC) hypothesis, stem-like CTCs might represent a potential source for cancer relapse and distant metastasis. Thus, identification of stem-like metastasis-initiating CTC-subset may provide useful clinically prognostic information...
October 11, 2016: Oncotarget
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