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More than 14,000 people die from invasive transitional cell carcinoma (TCC) of the urinary bladder yearly in the United States. Cyclooxygenase (COX)-inhibiting drugs are emerging as potential antitumor agents in TCC. The optimal in vitro or in vivo systems to investigate COX inhibitor antitumor effects have not been defined. The purpose of this study was to determine COX-1 and COX-2 expression and antitumor effects of COX inhibitors in human TCC cell lines (HT1376, RT4, and UMUC3 cells) and xenografts derived from those cell lines. COX-2 expression (Western blot, immunocytochemistry) was high in HT1376, modest in RT4, and absent in UMUC3 cells in vitro. Similarly, COX-2 expression was noted in RT4 but not UMUC3 xenografts. COX-2 expression in HT1376 xenografts was slightly lower than that observed in vitro. None of four COX inhibitors evaluated (celecoxib, piroxicam, valeryl salicylate, and NS398) reduced TCC growth in standard in vitro proliferation assays at concentrations that could be safely achieved in vivo (V5 Mmol/L). Higher celecoxib concentrations (z50 Mmol/L) inhibited proliferation and induced apoptosis in all three cell lines. Celecoxib or piroxicam treatment in athymic mice significantly delayed progression of HT1376 xenografts, which express COX-2, but not UMUC3 xenografts that lack COX-2 expression. In conclusion, standard in vitro assays were not useful in predicting COX inhibitor antitumor effects observed in vivo. Athymic mice bearing TCC xenografts provide a useful in vivo system for COX inhibitor studies. Results of this study provide justification for further evaluation of COX inhibitors as antitumor agents against TCC. [Mol Cancer Ther 2006;5(2):329 -36]

Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.

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BackgroundTracheobronchial foreign body aspiration in children is a life-threatening, emergent situation. Currently, the use of fiberoptic bronchoscopy for removing foreign bodies is attracting increasing attention. Oxygen desaturation, body movement, laryngospasm, bronchospasm, and breath-holding are common adverse events during foreign body removal. Dexmedetomidine, as a highly selective α2-adrenergic agonist, produces sedative and analgesic effects, and does not induce respiratory depression. We hypothesized that intranasal dexmedetomidine at 1 μg kg − 1 administered 25 min before anesthesia induction can reduce the incidence of adverse events during fiberoptic bronchoscopy under inhalation general anesthesia with sevoflurane.MethodsIn all, 40 preschool-aged children (6–48 months) with an American Society of Anesthesiologists physical status of I or II were randomly allocated to receive either intranasal dexmedetomidine at 1 μg·kg − 1 or normal saline at 0.01 ml kg− 1 25 min before anesthesia induction. The primary outcome was the incidence of perioperative adverse events. Heart rate, respiratory rate, parent-child separation score, tolerance of the anesthetic mask, agitation score, consumption of sevoflurane, and recovery time were also recorded.ResultsFollowing pre-anesthesia treatment with either intranasal dexmedetomidine or saline, the incidences of laryngospasm (15% vs. 50%), breath-holding (10% vs. 40%), and coughing (5% vs. 30%) were significantly lower in patients given dexmedetomidine than those given saline. Patients who received intranasal dexmedetomidine had a lower parent–child separation score (P = 0.017), more satisfactory tolerance of the anesthetic mask (P = 0.027), and less consumption of sevoflurane (38.18 ± 14.95 vs. 48.03 ± 14.45 ml, P = 0.041). The frequency of postoperative agitation was significantly lower in patients given intranasal dexmedetomidine (P = 0.004), and the recovery time was similar in the two groups.ConclusionsIntranasal dexmedetomidine 1 μg·kg− 1, with its sedative and analgesic effects, reduced the incidences of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy for FB removal. Moreover, it reduced postoperative agitation without a prolonged recovery time.Trail registrationThe study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017273) on July 20, 2018.

The regulation of cell proliferation, differentiation and immunomodulation are affected by 1,25(OH)2D3. However, its function during apoptosis and oxidative stress in human peritoneal mesothelial cells (HPMCs) remains unknown. The aim of the present study was to investigate whether the regulation of apoptosis and oxidative stress have therapeutic relevance in peritoneal dialysis (PD) therapy. The present study investigated the effects of 1,25(OH)2D3 on high glucose (HG)-induced apoptosis and reactive oxygen species (ROS) production in HPMCs, and examined the underlying molecular mechanisms. Flow cytometry and western blotting were performed to detect cell apoptosis, 2,7-dichlorofluorescein diacetate was used to measure reactive oxygen species production and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to measure cell viability. The results of the present study demonstrated that exposure to HG increased apoptosis and ROS production in HPMCs, whereas pretreatment with 1,25(OH)2D3 significantly inhibited HG‑induced apoptosis and ROS production. Further analysis revealed that 1,25(OH)2D3 facilitated cell survival via the MAPK/P38 pathway. The results of the present study indicate that 1,25(OH)2D3 inhibits apoptosis and ROS production in HG‑induced HPMCs via inhibition of the MAPK/P38 pathway.

Epithelial-mesenchymal transition (EMT) has been recognized to accelerate peritoneal membrane dysfunction. 1,25(OH)2D3/vitamin D receptor (VDR) is important for preventing various types of EMT in vivo. However, its function on EMT and inflammation of human peritoneal mesothelial cells (HPMCs) remains to be elucidated. Therefore, the present study investigated the effects of 1,25(OH)2D3/VDR on high glucose (HG)‑induced EMT and inflammation in HPMCs and the underlying molecular mechanism. It was determined that HG reduced VDR expression, increased inflammatory cytokine expression, including transforming growth factor β (TGFβ) and interleukin‑6 (IL‑6) and phosphorylated‑SMAD family member 3 (p‑Smad3) expression. EMT was promoted as the expression level of the epithelial marker E‑cadherin was reduced, whereas expression levels of the mesenchymal markers α‑SMA and FN were increased. 1,25(OH)2D3 pretreatment inhibited the expression of inflammatory cytokines in HPMCs and attenuated HG‑induced EMT, possibly through inhibition of the TGFβ/Smad pathway by binding to its receptor VDR.