174 research outputs found

    Slow magnetic dynamics and hysteresis loops of a bulk ferromagnet

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    Magnetic dynamics of a bulk ferromagnet, a new single crystalline compound Co7(TeO3)4Br6, was studied by ac susceptibility and the related techniques. Very large Arrhenius activation energy of 17.2 meV (201 K) and long attempt time (2x10^(-4)s) span the full spectrum of magnetic dynamics inside a convenient frequency window, offering a rare opportunity for general studies of magnetic dynamics. Within the experimental window the ac susceptibility data build almost ideally semicircular Cole-Cole plots. Comprehensive study of experimental dynamic hysteresis loops of the compound is presented and interpreted within a simple thermal-activation-assisted spin lattice relaxation model for spin reversal. Quantitative agreement between the experimental results and the model's prediction for dynamic coercive field is achieved by assuming the central physical quantity, the Debye relaxation rate, to depend on frequency, as well as on the applied field strength and sample temperature. Cross-over between minor- to major hysteresis loops is carefully analyzed. Low-frequency limitations of the model, relying on domain wall pinning effects, are experimentally detected and appropriately discussed.Comment: A paragraph on dynamical-hysteresis assymetry added, text partially revised; Accepted in Physical Review

    Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities

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    The Rho/ROCK pathway is involved in numerous pivotal cellular processes that have made it an area of intense study in cancer medicine, however, Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are yet to make an appearance in the clinical cancer setting. Their performance as an anti-cancer therapy has been varied in pre-clinical studies, however, they have been shown to be effective vasodilators in the treatment of hypertension and post-ischaemic stroke vasospasm. This review addresses the various roles the Rho/ROCK pathway plays in angiogenesis, tumour vascular tone and reciprocal feedback from the tumour microenvironment and explores the potential utility of ROCK inhibitors as effective vascular normalising agents. ROCK inhibitors may potentially enhance the delivery and efficacy of chemotherapy agents and improve the effectiveness of radiotherapy. As such, repurposing of these agents as adjuncts to standard treatments may significantly improve outcomes for patients with cancer. A deeper understanding of the controlled and dynamic regulation of the key components of the Rho pathway may lead to effective use of the Rho/ROCK inhibitors in the clinical management of cancer

    Physics of cancer spreading through epithelium

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    Many cancers spread across the epithelium and physics is needed to describe the process. Cell dynamics at the normal epithelium/cancer biointerface play a crucial role in the progression of the disease. An altered arrangement of epithelial cells significantly impacts progression, so that a detailed understanding of the biological and physical mechanisms governing the interface dynamics provides a promising basis for cancer prevention. The biological mechanisms involve cell signalling and gene expression, while the physical mechanisms are associated with the interplay between physical properties such as the epithelium-cancer interfacial tension, the epithelial surface tension, and the compressive stress within the epithelium. Despite extensive in vitro research on epithelium/cancer co-cultured cell systems, the influence of these physical parameters on cell reorganization remains incomplete. This review provides an account of what is known about the physical processes involved in cell reorganization within epithelium/cancer cell clusters and the dissemination of cancer within co-cultured systems

    Epithelial cell-cell interactions in an overcrowded environment: jamming or live cell extrusion

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    Epithelial tissues respond strongly to the mechanical stress caused by collective cell migration and are able to regulate it, which is important for biological processes such as morphogenesis, wound healing, and suppression of the spread of cancer. Compressive, tensional, and shear stress components are produced in cells when epithelial monolayers on substrate matrices are actively or passively wetted or de-wetted. Increased compressive stress on cells leads to enhanced cell-cell interactions by increasing the frequency of change the cell-cell distances, triggering various signalling pathways within the cells. This can ultimately lead either to cell jamming or to the extrusion of live cells. Despite extensive research in this field, it remains unclear how cells decide whether to jam, or to extrude a cell or cells, and how cells can reduce the compressive mechanical stress. Live cell extrusion from the overcrowded regions of the monolayers is associated with the presence of topological defects of cell alignment, induced by an interplay between the cell compressive and shear stress components. These topological defects stimulate cell re-alignment, as a part of the cells’ tendency to re-establish an ordered trend of cell migration, by intensifying the glancing interactions in overcrowded regions. In addition to individual cell extrusion, collective cell extrusion has also been documented during monolayer active de-wetting, depending on the cell type, matrix stiffness, and boundary conditions. Cell jamming has been discussed in the context of the cells’ contact inhibition of locomotion caused by cell head-on interactions. Since cell-cell interactions play a crucial role in cell rearrangement in an overcrowded environment, this review is focused on physical aspects of these interactions in order to stimulate further biological research in the field

    Physical aspects of epithelial cell-cell interactions : hidden system complexities

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    The maintenance of homeostasis and the retention of ordered epithelial cell self-organization are essential for morphogenesis, wound healing, and the spread of cancer across the epithelium. However, cell-cell interactions in an overcrowded environment introduce a diversity of complications. Such interactions arise from an interplay between the cell compressive and shear stress components that accompany increased cell packing density. They can lead to various kinds of cell rearrangement such as: the epithelial-to-mesenchymal cell state transition; live cell extrusion; and cell jamming. All of these scenarios of cell rearrangement under mechanical stress relate to changes in the strengths of the cell-cell and cell-matrix adhesion contacts. The objective of this review study is twofold: first, to provide a comprehensive summary of the biological and physical factors influencing the effects of cell mechanical stress on cell-cell interactions, and the consequences of these interactions for the status of cell-cell and cell-matrix adhesion contacts; and secondly, to offer a bio-physical/mathematical analysis of the aforementioned biological aspects. By presenting these two approaches in conjunction, we seek to highlight the intricate nature of biological systems, which manifests in the form of complex bio-physical/mathematical equations. Furthermore, the juxtaposition of these apparently disparate approaches underscores the importance of conducting experiments to determine the multitude of parameters that contribute to the development of these intricate bio-physical/mathematical models

    Clinical and molecular characterization of HER2 amplified-pancreatic cancer

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    <p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt
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