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      Quartz crystal microbalance based biosensors for detecting highly metastatic breast cancer cells via their transferrin receptors

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          Abstract

          The high sensitivity of the QCM sensor is combined with selectivity of receptor–ligand interactions to construct a biosensor which would discriminate breast cancer cells with high metastatic power from those of low or no metastatic potential to develop a simple, fast and efficient system to be used in breast cancer diagnosis.

          Abstract

          A quartz crystal microbalance (QCM) biosensor was developed to detect highly metastatic breast cancer cells by functionalizing the gold sensor surface with transferrin attachment. MDA-MB 231 breast cancer cells with high and MCF 7 cells with low metastatic potential and transferrin expression were used. Serum starved MDA-MB-231 cells were used as control cells. First, poly(2-hydroxyethyl methacrylate) (PHEMA) nanoparticles were prepared by mini-emulsion polymerization of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA). Nanoparticles were characterized with a zeta-sizer and then their suspension is dropped on the surface of the QCM and the dried QCM surface was modified further by activation with carbodiimide and transferrin attachment. The QCM biosensor was analyzed by using atomic force microscopy (AFM), ellipsometry, Fourier transform infrared spectrophotometry (FTIR) and contact angle measurements. The cells were applied to the derivatized QCM sensor to investigate the affinity and binding kinetics. The nanoparticles and transferrin were found to form a monolayer on the QCM surface. Binding kinetics were best fitted to the Langmuir–Freundlich adsorption model. The QCM signal was correlated well with the number of transferrin receptors on cells. It is concluded that the QCM biosensor functioning via transferrin receptor interactions may be used to detect breast cancer cells with high metastatic potential.

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          Regulation of cellular iron metabolism

          Iron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron–sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in cytosolic ferritin. Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.
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            Detecting Circulating Tumor Cells: Current Challenges and New Trends

            Circulating tumor cells (CTCs) in the blood stream play a critical role in establishing metastases. The clinical value of CTCs as a biomarker for early cancer detection, diagnosis, prognosis, prediction, stratification, and pharmacodynamics have been widely explored in recent years. However, the clinical utility of current CTC tests is limited mainly due to methodological constraints. In this review, the pros and cons of the reported CTC assays are comprehensively discussed. In addition, the potential of tumor cell-derived materials as new targets for CTC detection, including circulating tumor microemboli, cell fragments, and circulating DNA, is evaluated. Finally, emerging approaches for CTC detection, including telomerase-based or aptamer-based assays and cell functional analysis, are also assessed. Expectantly, a thorough review of the current knowledge and technology of CTC detection will assist the scientific community in the development of more efficient CTC assay systems.
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              Biosensor technology: recent advances in threat agent detection and medicine.

              Biosensors are of great significance because of their capability to resolve a potentially large number of analytical problems and challenges in very diverse areas such as defense, homeland security, agriculture and food safety, environmental monitoring, medicine, pharmacology, industry, etc. The expanding role of biosensing in society and a real-world environment has led to an exponential growth of the R&D efforts around the world. The world market for biosensor devices, according to Global Industry Analysts, Inc., is expected to reach $12 billion by 2015. Such expedient growth is driven by several factors including medical and health problems, such as a growing population with a high risk of diabetes and obesity, and the rising incidence of chronic diseases such as heart disease, stroke, cancer, chronic respiratory diseases, tuberculosis, etc.; significant problems with environmental monitoring; and of course serious challenges in security and military applications and agriculture/food safety. A review paper in the biosensor technology area may be structured based on (i) the principles of detection, such as the type of transducer platform, bioanalytical principles (affinity or kinetic), and biorecognition elements origin/properties (i.e. antibodies, enzymes, cells, aptamers, etc.), and (ii) the application area. This review follows the latter strategy and focuses on the applications. This allows discussion on how different sensing strategies are brought to bear on the same problem and highlights advantages/disadvantages of these sensing strategies. Given the broad range of biosensor related applications, several particularly relevant areas of application were selected for review: biological threat agents, chemical threat agents, and medicine.
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                Author and article information

                Journal
                AMNECT
                Analytical Methods
                Anal. Methods
                Royal Society of Chemistry (RSC)
                1759-9660
                1759-9679
                2016
                2016
                : 8
                : 1
                : 153-161
                Affiliations
                [1 ]Nanotechnology and Nanomedicine Division
                [2 ]Hacettepe University
                [3 ]Ankara
                [4 ]Turkey
                [5 ]Biochemistry Department
                [6 ]Faculty of Medicine
                [7 ]Chemistry Technology Division
                [8 ]Abant İzzet Baysal University
                [9 ]Bolu
                [10 ]Chemistry Department
                Article
                10.1039/C5AY02898A
                4dcbf463-2261-4199-890d-77ee6a038a60
                © 2016
                History

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