Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.
Aim To evaluate the effect of sugammadex compared with neostigmine on speed and quality of recovery after rocuronium neuromuscular blockade (NMB) in geriatric patients undergoing posterior lumbar spine surgery. Methods This randomized controlled study at a tertiary academic medical center involved 40 patients (age ≥65 years, ASA PS II/III) scheduled for elective surgery under general anesthesia. Patients were randomized to sugammadex or neostigmine for reversal of moderate NMB with rocuronium. The primary outcome was recovery time from NMB after surgery to a train-of-four (TOF) ratio ≥0.9 measured at the adductor pollicis (TOF-Watch ® SX). Secondary outcomes included hemodynamic change after administration of reversal agent (heart rate, blood pressure, dysrhythmia), time to extubation, pain medication requirement, time to first ambulation, and length of postanesthesia care unit (PACU) and total hospital stay. Results Sugammadex (4 ± 2.2 min) compared with neostigmine reversal (26.3 ± 17.5 min) was on average 22 min faster (95% CI 14.1-30.5; P <0.001) with less variability (range 2-11 min vs 5-72 min). The groups significantly differed in time for tracheal extubation, response to verbal commands (open eyes, squeeze hand, lift head), and operating room exit. However, they had similar PACU stay, time to first ambulation, total hospital stay, postoperative pain, and opioid use. Sugammadex had less hemodynamic variability than neostigmine. No patient developed treatment-emergent dysrhythmias. Conclusion Sugammadex reversal significantly hastened NMB recovery compared with neostigmine reversal in geriatric patients. It significantly decreased operating room time but not PACU time or hospital stay. ClinicalTrial.gov identification number NCT03112993
Ovarian cancer is the leading cause of cancerassociated mortality in the female reproductive system. Interleukin (IL)-33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL-33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL-33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL-33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase-3 activity kit were all used to evaluate the direct effects of IL-33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription-polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL-33; however, the relative caspase-3 activity in cancer cells was decreased in the presence of IL-33. Molecular mechanism studies revealed that the pro-proliferative effect of IL-33 on cancer cells was associated with decreased levels of p27, and the anti-apoptotic effect of IL-33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAILR1). Therefore, IL-33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti-tumor effort in pancreatic cancer, the results of the present study indicated that IL-33 exhibited a significant onco-promoting effect on ovarian cancer. Accordingly, the inhibition of IL-33 may be a promising therapeutic strategy for ovarian cancer.
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