1,720,969 research outputs found
Integrating Metabolic, Neo-Angiogenic, and HER2-Targeted Imaging to Characterize Breast Cancer in Preclinical Models
Get PDFBackground: Breast cancer is a highly heterogeneous disease, necessitating advanced imaging techniques for effective diagnosis and treatment. The visualization of metabolic activity, angiogenesis, and biomarkers such as HER2 expression provides critical insights into tumor behavior. This study integrates three molecular imaging approaches to explore tumor heterogeneity, focusing on metabolic activity, angiogenesis, their possible relationship, and HER2 expression in preclinical breast cancer models.
Materials and Methods:(1) The relationship between metabolic activity and angiogenesis was assessed using [18F]FDG and [68Ga]Ga-NODAGA-c(RGDfK)2 (RGD) PET imaging in fast-growing 4T1 and slow-growing MDA-MB-HER2+ xenografts. Tumor/muscle ratios were analyzed using the Muscle-Spacing Correction Method. (2) HER2-targeted imaging with [52Mn]Mn-DOTAGA(anhydride)-trastuzumab was evaluated in orthotopic and ectopic MDA-MB-HER2+ and MDA-MB-468 (HER2-negative) xenografts. Tumor-to-background ratios were calculated, with melanoma xenografts serving as a specificity control. (3) A novel Mn(II) chelator, BPPA, was compared to DOTAGA-pSCN-Bn for [52Mn]Mn-trastuzumab labeling. Tumor-to-background ratios and tumor uptake were analyzed in 4T1 (HER2−) and MDA-MB-HER2+ xenografts.
Results: (1) In the 4T1 group, both FDG and RGD imaging revealed highly heterogeneous tumor structures with correlations between uptake and tumor growth. FDG and RGD uptake showed relative linear correlations in all the tumors, with 4T1 showing higher FDG/RGD ratios compared to MDA-MB-HER2+. (2) [52Mn]Mn-DOTAGA(anhydride)-trastuzumab demonstrated higher tumor-to-background ratios in orthotopic HER2-positive tumors, showing consistently superior uptake compared to ectopic HER2-positive tumors, HER2-negative tumor and melanoma at all-time points. (3) The novel BPPA chelator significantly outperformed DOTAGA-pSCN-Bn in tumor imaging with [52Mn]Mn-BPPA-trastuzumab showing significantly superior tumor-to-background ratios. Using BPPA tracer, HER2+ tumor uptake remained higher than HER2− at all time points, with a 3–4 fold higher contrast over HER2− tumors by day 7, establishing its potential for extended imaging windows and earlier detection compared to the DOTAGA chelator.
Conclusion: Integrating metabolic, angiogenic, and receptor-targeted imaging offers a comprehensive approach to characterizing breast cancer heterogeneity. The combination of [18F]FDG, RGD, and [52Mn]Mn-based radiotracers, especially with BPPA chelator, demonstrates the potential to improve imaging precision and optimize treatment strategies
Novel ultrasound techniques
No full textElastography is a novel ultrasound technique which has been gaining a lot of attention in recent years. It is still a developing ultrasound technique that has evolved into a clinically useful technique in ultrasound machines. It provides stiffness measurements of investigated tissues, with four main methods in our days. Since many pathological conditions alter the tissues’ structure and change stiffness, this modality can improve diagnosis with greater confidence.általános orvosangolegységes, osztatla
Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states
No full textForced-rupture of Cell-Adhesion Complexes Reveals abrupt switch between two Brittle States
No full textAbstractCell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments using atomic force spectroscopy on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate (rf) and constant force (F) simulations using the Self-Organized Polymer (SOP) model to describe the mechanism of ligand rupture from CACs. The simulations reproduce the major experimental finding on the kinetics of the rupture process, namely, the dependence of the most probable rupture forces (f∗s) on ln rf (rf is the loading rate) exhibits two distinct linear regimes. The first, at low rf, has a shallow slope whereas the the slope at high rf is much larger, especially for LFA-1/ICAM-1 complex with the transition between the two occurring over a narrow rf range. Locations of the two transition states (TSs), extracted from the simulations show an abrupt change from a high value at low rf or F to a low value at high rf or F. This unusual behavior in which the CACs switch from one brittle (TS position is a constant over a range of forces) state to another brittle state is not found in forced-rupture in other protein complexes. We explain this novel behavior by constructing the free energy profiles, F (Λ)s, as a function of a collective reaction coordinate (Λ), involving many key charged residues and a critical metal ion (M g2+). The TS positions in F(Λ), which quantitatively agree with the parameters extracted using the Bell-Evans model, change abruptly at a critical force, demonstrating that it, rather than the molecular extension is a good reaction coordinate. Our combined analyses using simulations performed in both the pulling modes (constant rf and force) reveal a new mechanism for the two loading regimes observed in the rupture kinetics in CACs.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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