Int J Med Sci
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Background: Targeted therapy of Neurofibromatosis type 1 (NF1) related plexiform neurofibroma (pNF) aiming at MEK molecule has not demonstrated a convincing result for complete disease inhibition, probably due to other signal pathways crosstalk. Our previous study revealed an increased nuclear translocation of YAP molecule in NF1 related pNF. Herein, we decided to further investigate the therapeutic relations of YAP interference during the MEK treatment against NF1 related pNF. ⋯ Additionally, when combined treatments were performed based on verteporfin and selumetinib, synergistic effects were observed on cytotoxicity of NF1 related pNF tumor cells in vitro and in vivo xenograft models. Conclusion: YAP inhibition can effectively sensitize NF1 related pNF tumor cells to selumetinib. Dual targeting of YAP and MEK might be a promising therapeutic strategy for treating NF1 related pNF.
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Observational Study
Characteristic of Apparent Diffusion Coefficient and Time Intensity Curve Analysis of Dynamic Contrast Enhanced MRI in Osteosarcoma Histopathologic Subtypes.
Background: According to WHO criteria, osteosarcoma (OS) consists of various histopathological subtypes. Thus, contrast-enhanced MRI is a very useful modality in the diagnosis and evaluation of osteosarcoma. Magnetic resonance imaging with dynamic contrast enhancement (DCE-MRI) studies was used to determine the apparent diffusion coefficient (ADC) value and the slope of the time-intensity curve (TIC). ⋯ This study found a significant correlation between the mean of ADC value and the OS histopathologic results as well as the correlation between the mean of ADC value and ME. Conclusion: The various types of osteosarcoma have a characteristic of radiological appearances which may similar to some bone tumor entities. The analysis of ADC values and TIC curves using % slope and ME of osteosarcoma subtypes can improve the accuracy of diagnosis as well as the monitoring of the treatment response and the disease progression.
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Introduction: The proinflammatory cytokine interleukin-4 (IL-4) induces mucus hypersecretion by human airway epithelial cells and the MAP kinase signalling pathway may be important in terms of IL-4-induced MUC5AC gene expression. Lipoxin A4 (LXA4) is an arachidonic acid-derived mediator that promotes inflammation by binding to the anti-inflammatory receptors (ALXs) or the formyl-peptide receptor like-1 (FPRL1) protein expressed by airway epithelial cells. Here, we explore the effects of LXA4 on IL-4-induced mucin gene expression in, and secretion from, human airway epithelial cells. ⋯ LXA4 suppressed IL-4-induced MUC5AC and 5B gene and protein expression by interacting with the IL4 receptor and mitogen-activated protein kinase (MAPK) pathway, including both phospho-p38 MAPK and phospho-extracellular signal-regulated kinase (phospho-ERK). IL-4 and LXA4 increased and decreased, respectively, the number of cells that stained with anti-MUC5AC and 5B antibodies. Conclusions: LXA4 may regulate mucus hypersecretion induced by IL4 in human airway epithelial cells.
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Background: Cytomegalovirus (CMV) reactivation is a common complication in patients undergoing allogeneic stem cell transplantation. However, the incidence of CMV reactivation is low after autologous stem cell transplantation (auto-SCT), and the prognostic value of CMV reactivation remains controversial. Moreover, reports on late CMV reactivation after auto-SCT are limited. ⋯ The predictive risk model showed good discrimination, with an area under the curve of 0.872 (standard error, 0.062; P < 0.001). Conclusions: Late CMV reactivation was an independent risk factor for inferior OS, whereas early CMV reactivation was associated with better survival in patients with multiple myeloma. This risk prediction model could be helpful in identifying high-risk patients who require monitoring for late CMV reactivation and potentially benefit from prophylactic or preemptive therapy.
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Zirconia and polyetheretherketone (PEEK) are two biomaterials widely investigated as substitute for metals in oral prosthetic rehabilitation. To achieve a proper biomechanical behavior, the prosthetic biomaterials must ensure a good resistance to loads, as this is a crucial characteristic enabling their use in dental applications. The aim of this study was to investigate differences in the fracture resistance of different biomaterials in an experimental environment: fixed partial dentures (FPDs) screwed in a prototype of biomimetic mandible. 10 Samples of FPDs were allocated in 2 groups (A and B): Group A (n=5) involved FPDs in zirconia-ceramic, and Group B (n=5) involved FPDs in PEEK-composite. ⋯ Zirconia-ceramic FDPs were the samples reporting the worst results, showing a lower value of vertical displacement with respect to PEEK-based samples. The micro-CT results have further confirmed the preliminary results previously described. This in vitro study aims to give analytic data on the reliability of PEEK as a reliable and strong biomaterial for prosthetic treatments.