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Background: It remains unclear whether deep neuromuscular blockade results in better postoperative recovery than does moderate neuromuscular blockade. Therefore, in this study, we aimed to compare the effects of deep neuromuscular blockade and moderate neuromuscular blockade on the quality of postoperative recovery in patients undergoing robotic gastrectomy.Methods: In this prospective, double-blind, single-center randomized controlled superiority trial with two parallel groups, 56 adult patients (19-80 years) scheduled for elective robotic gastrectomy were randomly assigned to a moderate neuromuscular blockade group or a deep neuromuscular blockade group in a 1:1 ratio. In the deep and moderate neuromuscular blockade groups, the infusion rate for rocuronium was adjusted to maintain a post-tetanic count of 1-2 or a train-of-four count of 1-2, respectively. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. Secondary outcomes included the QoR-40 score on postoperative day 2, intraoperative hemodynamic data, intraoperative respiratory data, visual analog scale score for pain, postoperative incidences of nausea and vomiting, postoperative rescue analgesic use, and postoperative rescue antiemetic use.Results: The postoperative QoR-40 score was similar between the two groups on postoperative days 1 and 2. Moreover, the two groups showed no differences in intraoperative hemodynamic and respiratory data or postoperative pain, nausea and vomiting, and rescue medication use.Conclusion: Our findings suggest that the quality of recovery after robotic gastrectomy is similar for deep and moderate neuromuscular blockade. Therefore, deep neuromuscular blockade during robotic gastrectomy may be unnecessary, at least in patients with normal body mass index. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence and risk factors of intestinal injury during gynecologic surgery for benign diseases, based on a national database., Method: The study cohort was generated by extracting patients with operation codes for benign gynecologic diseases from the Health Insurance Review & Assessment Service National Inpatient Sample from 2009 to 2018. After analyzing the incidence of bowel injury during gynecologic surgery, a multivariate analysis was performed to identify the associated risk factors for bowel injury., Results: Among 81 451 patients who underwent gynecologic surgery for benign diseases, the incidence of bowel injury was 6.14 per 1000 women. The risk of bowel injury decreased with laparoscopy (odds ratio [OR] 0.54; 95% confidence interval [CI] 0.41-0.69; P < 0.001) and increased with subtotal hysterectomy (OR 2.83; 95% CI 1.79-4.46; P < 0.001) and adnexectomy (OR 2.83; 95% CI 1.93-4.16; P < 0.001). Old age, higher Charlson comorbidity index, low socioeconomic status, and a higher clinic grade were associated with a higher risk of bowel injury., Conclusion: This study revealed the incidence of bowel injury during benign gynecologic surgery in a Korean national population-based cohort. The risk of bowel injury increased with open surgery, subtotal hysterectomy, and adnexectomy., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: CCAAT/enhancer-binding protein beta (C/EBPbeta) is a transcription factor and consists of three isoforms, transcription-activating A/B (C/EBPbeta-AB) and transcription inhibitory C (C/EBPbeta-C). We previously reported that C/EBPbeta-C was predominantly expressed in hormone-dependent LNCaP cells, while C/EBPbeta-AB forms were predominant in hormone-independent prostate cancer (HI-PCa) cells., Methods: Reporter gene analysis was performed to investigate transcriptional activity of C/EBPbeta on metastatic gene expression upon TNF-alpha treatment. NF-kappaB activation and C/EBPbeta protein upregulation were determined by immunoblotting. WST assay was used to determine the role of C/EBPbeta in TNF-alpha-induced cell death., Results: We first determined that the C/EBPbeta-C overexpression or siRNA-mediated C/EBPbeta depletion decreased TNF-alpha-induced promoter activities of Bfl-1, IL-6, and IL-8 genes. IL-6 and IL-8 are autocrine growth factors of HI-PCa cells and Bfl-1 is an anti-apoptotic protein whose function in prostate cancer is yet to be determined. Secondly, we determined differential regulation of C/EBPbeta by TNF-alpha. In DU-145 cells, C/EBPbeta was upregulated by TNF-alpha, but downregulated in LNCaP cells, although NF-kappaB was activated in both cells. This result suggested cell-type specific activation of signaling pathways leading to C/EBPbeta upregulation, which was distinct from that leading to NF-kappaB activation. Most importantly, C/EBPbeta depletion decreased cell growth and sensitized DU-145 cells to TNF-alpha-induced cell death. Conversely, overexpression of C/EBPbeta-A in LNCaP cells increased resistance to TNF-induced cell death and TNF-induced promoter activities of IL-6 and Bfl-1., Conclusion: Our study, for the first time, demonstrated that C/EBPbeta regulated cell growth and conferred TNF-alpha resistance to PCa cells, in part, via regulation of metastatic gene expression. Prostate 69: 1435-1447, 2009. (c) 2009 Wiley-Liss, Inc.

Background: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is commonly overexpressed in prostate cancer (PCa) cells. As PCa cells are known to survive serum deprivation, we investigated the effect of prolonged serum deprivation on HIF-1 alpha expression, and the function of HIF-1 alpha in regulating the survival of normoxic serum-deprived PCa cells., Methods: HIF-1 alpha protein was assessed by immunoblots. Cell viability and proliferation were assessed by trypan blue assay and flow cytometric analysis. Transcriptional activity was assessed by luciferase reporter assay and RT-PCR. HIF-1 alpha expression was suppressed with siRNA. Activities of HIF-1 alpha-target genes were inhibited with neutralizing antibody., Results: Prolonged serum deprivation is a potent inducer of HIF-1 alpha in PC-3 and LNCaP PCa cells, despite normal oxygen conditions. In contrast, cells grown in the presence of serum did not show HIF-1 alpha protein accumulation. Moreover, HIF-1 alpha protein increase during serum deprivation correlated with increased cell survival, while suppression of HIF-1 alpha expression significantly decreased PCa cell viability. Our results further demonstrate that HIF-1 alpha protein increase is due to increased HIF-1 alpha protein synthesis. First, there was no significant increase in HIF-1 alpha mRNA. Secondly, cycloheximide, a protein synthesis inhibitor, prevented HIF-1 alpha protein increase in serum-deprived PCa cells. Moreover, the expression of HIF-1 alpha-target genes, VEGF and IGF-2, was concomitantly increased in serum-deprived PCa cells, while suppression of HIF-1 alpha expression significantly inhibited their induction. Furthermore, inhibition of IGF-2 activity resulted in a significant decline in PCa cell survival., Conclusion: PCa cells counteract the stress of prolonged serum deprivation by upregulating HIF-1 alpha protein which increases IGF-2 expression to promote cell survival., ((c) 2008 Wiley-Liss, Inc.)

Background: C/EBP beta is a transcription factor regulating key biological processes including cellular growth and differentiation and its increased expression correlates with tumor invasiveness. Recently, the increased expression of C/EBP beta was reported in proliferative inflammatory atrophy of the prostate, associating with increased COX-2 expression and androgen receptor (AR) downregulation., Methods: C/EBP beta expression was determined in DU-145, PC-3 and LNCaP cells by immunoblotting. Transient transfection of C/EBP beta expression vectors was performed to investigate translational regulation of its isoform expression. Reporter gene analysis was performed to investigate transcriptional activity of C/EBP beta on metastatic gene expression., Results: We determined that transcriptionally active, full-length C/EBP beta isoforms were dominantly expressed in hormone-independent DU-145 and PC-3 cells, while transcription-repressing truncated isoform was dominant in hormone-dependent LNCaP cells. Our results further showed lack of full-length isoform expression from the transiently transfected C/EBP beta expression vector in LNCaP cells compared to that in PC-3 cells transfected with the same vector, while the expression of truncated isoform was comparable in both cell lines. Interestingly, however, the most upstream initiation site A null mutation restored translation of full-length isoform in LNCaP cells. These results suggest that full-length C/EBP beta isoform expression in LNCaP cells may be suppressed at the upstream initiation sites, likely at site A. Most importantly, C/EBP beta overexpression significantly upregulated promoter activities of IL-8, COX-2, and anti-apoptotic Bfl-1 genes., Conclusions: Our study demonstrates that C/EBP beta is an important transcription factor upregulating metastatic gene expression and that its isoform expression is differentially regulated at the translational level in prostate cancer cells., ((c) 2008 Wiley-Liss, Inc.)

Background: One of the green tea components epigallocatechin-3-gallate (EGCG) significantly prevented the growth of prostate cancer cells. In this study, synergistic effect of EGCG and ibuprofen (EGCG+ibuprofen) was investigated to determine their anti-proliferative and pro-apoptotic action in DU-145 prostate cancer cells., Materials and Methods: Cell death analysis, immunoblotting, RT-PCR analysis, and caspase activity assay were used., Results: EGCG+ibuprofen treatment resulted in 90% growth inhibition, while ibuprofen or EGCG alone reduced cell numbers by 25% and 20%, respectively. EGCG+ibuprofen induced MAPK activation, caspase activation and the inhibition of Bfl-1 expression, all of which were blocked by the antioxidant, N-acetyl-L-cysteine (NAC). Moreover, addition of ceramide rescued the NAC-inhibited MAPK activation and pretreatment with the ceramide synthase inhibitor, fumonisin B1, reduced cell death., Conclusion: Our results suggest that in DU-145 prostate cancer cells: (i) EGCG+ibuprofen treatment has a synergistic effect on apoptosis, and (ii) oxidative stress, directly or indirectly via ceramide synthesis mediates pro-apoptotic signaling.

Background: Soy isoflavones, genistein, daidzein and glycitein, are thought to have beneficial effects on cancer prevention., Materials and Methods: We used cell cycle analysis, invasion assay and immunoblotting to determine the effects of genistein and glycitein on Jurkat T cells., Results: Glycitein inhibited Jurkat cell invasion at a level comparable to the inhibition by genistein. Both genistein and glycitein down-regulated MMP-13 proteolytic activity by 60-70% and MMP-8 expression. Caffeine could block G2/M arrest by genistein, but was unable to block the inhibition of invasion by genistein and glycitein. We also demonstrated that glycitein inhibited proteintyrosine phosphorylation in Jurkat cells., Conclusion: We determined, for the first time, that glycitein inhibited Jurkat cell invasion, in part through the down-regulation of MMP-13 activity and MMP-8 expression. Our findings also suggest that soy isoflavones may utilize different mechanisms to exert their effects on cell cycle progression and invasiveness of Jurkat cells.

Since it is known that a 307 bp fragment of the position specific regulatory element of human HOXA-7 contains two (DR3 and DR5) retinoic acid response elements (RAREs) at its 3' end, we constructed several deletion constructs containing different numbers of RAREs and examined their effects in vitro and in vivo. The 5' deletion constructs, BM112 and OM213, retaining both RAREs, were highly responsible (about 8 fold induction) for RA in F9 teratocarcinoma cells, versus NM307 (4-5 fold). The construct NS218, with both RAREs deleted but retaining the 5' sequences lost RA responsibility completely, whereas NR271, with one RARE(DR5) deleted retained a 50% inducibility (2.5 fold). In vivo transgenic analysis revealed that the constructs NM307 and NR271, but not OM213 nor BM112, directed the position specific expression pattern. Sequence analysis revealed that HOXA-7 enhancer sequences, including the RARE repeat sequences, were well conserved in human, mouse and chick. Part of the RAREs overlaps with the CDX1 binding site, and sequences of the DR3 RAREs were identical in this species. Two GAGA binding sites were also found to be strictly conserved. Because OM213, which had one GAGA site disrupted but retaining both RAREs, did not direct anterior boundary formation in transgenic mice, these results suggest the importance of the 5' 94 bp region, including the GAGA binding site, in anterior boundary formation and the involvement of the RARE in the rate of expression not in anterior boundary formation.