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Infections during first-line therapy for DLBCL are often associated with chemotherapy dose reductions and increased mortality. Systemic infections have also been suggested as beneficial promotors of immunological responses. However, whether there is an association between the timing of an infectious episode and outcome during treatment has not yet been clarified. We investigated how the occurrence and timing of infectious episodes during the 1st line of treatment for 'de novo' DLBCL influenced patient outcome. We used data on DLBCL patients from the Danish Lymphoma Registry, the Danish National Patient Registry and the Danish National Pathology Registry. Infections were categorized according to type (ICD-10) and time of occurrence after treatment start. 'Early' infections were defined as occurring between days 7-42 and 'late' infections between days 100-150 from treatment start. Patients experiencing both 'early and late' infections, were categorized separately. We used multivariable Cox regression and Kaplanicle is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment. selleck products © 2020 Wiley Periodicals, Inc.E-cadherin, a central component of the adherens junction (AJ), is a single-pass transmembrane protein that mediates cell-cell adhesion. The loss of E-cadherin surface expression, and therefore cell-cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)-derived cells (SW-480 and HT-29) with 2.0 mM metformin promoted a redistribution of cytosolic E-cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120-catenin, another core component of the AJs. Furthermore, E-cadherin and p120-catenin colocalized with β-catenin at cell-cell contacts. Western blot analysis of lysates of CRC-derived cells revealed a substantial metformin-induced increase in the level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840 , a modification associated with β-catenin/E-cadherin interaction. These modifications in E-cadherin, p120-catenin and β-catenin localization suggest that metformin induces rebuilding of AJs in CRC-derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118 . These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression. © 2020 Wiley Periodicals, Inc.Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson > 0·91, P 0·03% LSC) from LSClow ( less then 0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification. © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.INTRODUCTION To compare diagnostic performance of additional two-dimensional (2D) oblique coronal view and three-dimensional (3D) T2-weighted fast spin-echo(FSE) images for diagnosing injury of the anterior inferior tibiofibular (AiTFL) and anterior talofibular ligaments (ATFL). METHODS This study included 48 patients with ankle sprain who had undergone MRI using standard protocol and two additional sequences with 2D oblique coronal and 3D isotropic images, followed by arthroscopic surgery. Ligament injuries was subdivided by intact tendon, partial or complete tear. Retrospectively, two musculoskeletal radiologists respectively reviewed three image sets of MR including 2D axial image only (set 1), 2D axial and oblique coronal images (set 2), and 2D axial with 3D-isotropic images (set 3). Using arthroscopic findings as reference standard, diagnostic performances of both methods were analysed by the area under the curve (AUC). RESULTS Arthroscopy confirmed 13 AiTFL and 41 ATFL injuries. For AiTFL, when set 1 and set 3 were compared, AUC value was significantly higher for set 3 (P 0.05). For ATFL, both readers found there was no significant difference in AUC values between set 1 and set 3 and between set 2 and set 3. CONCLUSION Additional oblique coronal sequence demonstrated better diagnostic performance for AiTFL injury than conventional and isotropic imaging did. This sequence showed as much diagnostic accuracy as isotropic sequence for evaluation of ATFL injury. © 2020 The Royal Australian and New Zealand College of Radiologists.
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