Objectives The role of celecoxib in preventing and treating tumors has attracted broad attention in recent years because of its selective and specific inhibition of COX‐2 activity. We investigated the inhibitory effects and mechanisms of celecoxib combined with 5‐fluorouracil (5‐FU) on proliferation of squamous cell carcinoma cells in vivo and in vitro. Study Design Animal study and basic research. Methods SNU‐1041 and SNU‐1076 squamous cell lines and an orthotopic tongue cancer mouse model were used to study growth inhibition with 5‐FU enhanced by celecoxib. Sensitivity of cells to drug treatment was analyzed by the MTT assay, and generation of reactive oxygen species (ROS) was measured using dichlorofluorescein diacetate. Phosphorylation of AKT was detected by Western blotting. Survival analysis in the mouse model was assessed according to combination treatment with 5‐FU and celecoxib. Results Reactive oxygen species production in vitro was highest when celecoxib was administered 48 hours after 5‐FU treatment. 5‐FU–induced inhibition of cell proliferation was enhanced when combined with celecoxib, which was positively correlated with ROS production. Antioxidant treatment reversed 5‐FU–inhibited cell proliferation by up to 60%. Cotreatment with celecoxib and 5‐FU partially blocked AKT phosphorylation, although no significant changes in total AKT protein levels were detected. An increased survival time was observed in an orthotopic mouse model treated with a combination of celecoxib and 5‐FU compared to treatment with either agent alone. Conclusion Celecoxib may have an enhanced anticancer effect in combination with 5‐FU. Reactive oxygen species production may be a key mechanism in this combination therapy by inhibiting the AKT pathway. Level of Evidence N/A. Laryngoscope, 127:E117–E123, 2017
Hand massage can be a helpful nursing intervention for transradial percutaneous coronary intervention by reducing pain and discomfort to a considerable degree.
ObjectiveNeural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions.MethodsRats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[18F]-fluoro-D-glucose ([18F]-FDG) and [18F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([18F]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results.ResultsThe stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [18F]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human β2 microglobulin (a human cell marker) positive cells were visualized at the transplant site.ConclusionThese results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.
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