110 research outputs found

    Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival

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    <p>Abstract</p> <p>Background</p> <p>Heat shock proteins (HSPs) are ubiquitous, highly conserved proteins across all the species and play essential roles in maintaining protein stability within the cells under normal conditions, while preventing stress-induced cellular damage. HSPs were also overexpressed in various types of cancer, being associated with tumor cell proliferation, differentiation and apoptosis. The aim of the present study was to evaluate the clinical significance of HSP -27, -60, and -90 expression in gastric carcinoma.</p> <p>Methods</p> <p>HSP -27, -60, and -90 proteins expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival.</p> <p>Results</p> <p>HSP-27, -60, -90 proteins were abundantly expressed in gastric adenocarcinoma cases examined. HSP-27 expression was significantly associated with tumor size (pT, P = 0.026), the presence of organ metastases (pM, P = 0.046) and pStage (P = 0.041), while HSP-27 staining intensity with nodal status (pN, P = 0.042). HSP-60 expression was significantly associated with patients' sex (P = 0.011), while HSP-60 staining intensity with patients' age (P = 0.027) and tumor histopathological grade (P = 0.031). HSP-90 expression was not associated with any of the clinicopathological parameters examined; however, HSP-90 staining intensity was significantly associated with tumor size (pT, P = 0.020). High HSP-90 expression was significantly associated with longer overall survival times in univariate analysis (log-rank test, P = 0.033), being also identified as an independent prognostic factor in multivariate analysis (P = 0.026).</p> <p>Conclusion</p> <p>HSP-27, -60, and -90 were associated with certain clinicopathological parameters which are crucial for the management of gastric adenocarcinoma patient. HSP-90 expression may also be an independent prognostic indicator in gastric adenocarcinoma patients.</p

    In Vivo Tracking of Transplanted Mononuclear Cells Using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

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    BACKGROUND: Transplantation of mononuclear cells (MNCs) has previously been tested as a method to induce therapeutic angiogenesis to treat limb ischemia in clinical trials. Non-invasive high resolution imaging is required to track the cells and evaluate clinical relevance after cell transplantation. The hypothesis that MRI can provide in vivo detection and long-term observation of MNCs labeled with manganese contrast-agent was investigated in ischemic rat legs. METHODS AND FINDINGS: The Mn-labeled MNCs were evaluated using 7-tesla high-field magnetic resonance imaging (MRI). Intramuscular transplanted Mn-labeled MNCs were visualized with MRI for at least 7 and up to 21 days after transplantation in the ischemic leg. The distribution of Mn-labeled MNCs was similar to that of ¹¹¹In-labeled MNCs measured with single-photon emission computed tomography (SPECT) and DiI-dyed MNCs with fluorescence microscopy. In addition, at 1-2 days after transplantation the volume of the site injected with intact Mn-labeled MNCs was significantly larger than that injected with dead MNCs, although the dead Mn-labeled MNCs were also found for approximately 2 weeks in the ischemic legs. The area covered by CD31-positive cells (as a marker of capillary endothelial cells) in the intact Mn-MNCs implanted site at 43 days was significantly larger than that at a site implanted with dead Mn-MNCs. CONCLUSIONS: The present Mn-enhanced MRI method enabled visualization of the transplanted area with a 150-175 µm in-plane spatial resolution and allowed the migration of labeled-MNCs to be observed for long periods in the same subject. After further optimization, MRI-based Mn-enhanced cell-tracking could be a useful technique for evaluation of cell therapy both in research and clinical applications

    DNA Origami Characterized via Solid-State Nanopore: Insights into Nanostructure Dimensions, Rigidity and Yield

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    Due to their programmability via specific base pairing, self-assembled DNA origami structures have proven to be useful for a wide variety of applications, including diagnostics, molecular computation, drug delivery, and therapeutics. Measuring and characterizing these structures is therefore of great interest and an important part of quality control. Here, we show the extent to which DNA nanostructures can be characterized by a solid-state nanopore; a non-destructive, label-free, single-molecule sensor capable of electrically detecting and characterizing charged biomolecules. We demonstrate that in addition to geometrical dimensions, nanopore sensing can provide information on the mechanical properties, assembly yield, and stability of DNA nanostructures. For this work, we use a model structure consisting of a 3 helix-bundle (3HB), i.e. three interconnected DNA double helices using a M13 scaffold folded twice on itself by short DNA staple strands, and translocate it through solid-state nanopores fabricated by controlled breakdown. We present detailed analysis of the passage characteristics of 3HB structures through nanopores under different experimental conditions which suggest that segments of locally higher flexibility are present along the nanostructure contour that allow for the otherwise rigid 3HB to fold inside nanopores. By characterizing partially melted 3HB structures, we find that locally flexible segments are likely due to short staple oligomers missing from the fully assembled structure. The 3HB used herein is a prototypical example to establish nanopores as a sensitive, non-destructive, and label-free alternative to conventional techniques such as gel electrophoresis with which to characterize DNA nanostructures
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