Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1/2 pathway and cyclin D1 expression / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth.</p><p><b>METHODS</b>The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor (GR) antagonist RU486. Reverse transcription-polymerase chain reaction verified the expression of GR mRNA in DU145 cells.</p><p><b>RESULTS</b>Dexamethasone significantly inhibited DU145 cell proliferation at the G(0)/G(1) phase. Western blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade.</p><p><b>CONCLUSION</b>Dexamethasone suppresses DU145 cell proliferation and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy.</p>

Transcriptional expression of hypoxia/hypothermia-conditioned human endothelial cells and their interaction with monocytes / 中华器官移植杂志

Objective To characterize molecule profiling for hypoxia/hypothermia-conditioned human endothelial cells(EC),and to examine the hypothesis that the interaction between hypoxia/hy- pothermia-conditioned EC and monocytes plays a key role in early hypoxia/hypothermic reperfusion in- jury.Methods Human aortic EC were conditioned in hypoxia/hypothermia chamber at 4℃for 91) rain followed by 4 to 8 h re-warming at 37℃and then analyzed initially by RT-PCR to evaluate RNA transcripts.To examine early cellular interactions,a cellular adhesion study was performed using EC and fluorescence-conjugated DIO labeled purified human monocytes,and CD4~+ T cells as well as PB- MC.Interactions between PKH-26-labeled EC and these cells were carried out to determine EC mem- brane uptake by monocytes.Results RT-PCR analysis demonstrated that hypoxia/hypothermia-con- ditioned EC up-regulated RNA transcripts of inflammatory cytokines,ECE-1 and endothelin,co-stim- ulatory molecules,and adhesion molecules CD54.FACS showed minimal up-regulation of CD54 on hy- poxia-hypothermia-conditioned EC.Low level adhesion of purified CD4~+ T cells to resting and hypoxi- a/hypothermia-conditioned EC was noted.In contrast,high levels of monocyte adhesion to hypoxia/ hypothermia-conditioned EC were observed when compared to resting EC.EC membrane up-take by monocytes but not CD4~+ T cells was revealed by FACS,and the levels of EC membrane up-take were similar to those of the normal EC.Conclusions Hypoxia/hypothermia-conditioned EC demonstrated up-regulation of multiple RNA transcripts associated with inflammatory responses,cellular adhesion and co-stimulation.Human monocyte adhesion to hypoxia/hypothermia-conditioned EC was greater than T cells.Monocytes up-took EC membrane during their interaction.These findings suggest that the initial interaction between monocytes and hypoxia-hypothermia EC,but not T cells,may play a critical role during early reperfusion injury.

Presence of autoantibodies in sera of patients with sporadic idiopathic hypoparathyroidism / 中华检验医学杂志

Objective To explore whether autoreactive antibody presents in patients with sporadic idiopathic hypoparathyroidism(sIHP).Methods The subjects including 26 patients with sIHP and 112 genealogical members as well as 60 age-and sex-matched healthy controls.Anti-parathyroid antibodies in the sera were assayed by indirect immunofluorescence.The levels of calcium,phosphorus and magnesium as well as intact parathyroid hormone(iPTH)in the sera were tested.Results Positive autoantibodies against parathyroid tissue were demonstrated in 10 patients(38%)with sIHP,significantly higher than that of in genealogical members(10%,?~2=13.42,P