Von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has been unclear yet. The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labeling and quantitative real-time PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS cells were assessed by cell proliferation, colony formation, and migration. The clinical significance of miR-24 in OS patients was analyzed using Kaplan–Meier analyses and Pearson’s Chi-squared test. Here, we reported that the expression of vWF was significantly increased, but miR-24 was significantly decreased in OS tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63 and U2OS cells. However, the migration-inhibiting activity of miR-24 was predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression in human OS tissues was significantly associated with tumor metastasis and predicted a poor survival in OS patients. This work demonstrated that vWF, as a downstream effector of miR-24, played an important role in controlling OS cell progression. Target miR-24 or vWF, therefore, promises to be an effective biological target for OS treatment.
Treatment with immune checkpoint inhibitors (ICI) such as carrizumab leads to immune-mediated adverse effects including severe acute graft versus host disease (aGVHD) and secondary hemophagocytic syndrome (sHLH). Herein, we present two cases where aGVHD and sHLH developed after ICI administration, which was treated using methylprednisolone (MP). They developed high-grade fever complicated with liver dysfunction and diarrhea 1 day after ICI administration. Treatment with MP does not alleviate symptoms because of steroid resistance. Hyperbilirubinemia, rash with blisters, and watery diarrhea showed severe aGVHD. Hyperferritinemia, hypertriglyceridemia, and cytopenias suggested the diagnosis of HLH and met the criteria for sHLH diagnosis. They were thus administered intravenous high-dose MP, methotrexate (MTX), basiliximab, ruxolitinib, etc, which resolved these symptoms.
29 March 2020 in Clinical and Experimental Pharmacology and Physiology