The p53 and EGFR pathways are frequently altered in bladder cancers, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of
Small cell lung cancer (SCLC) is aggressive, with rapid growth and frequent bone metastasis; however, its detailed molecular mechanism remains poorly understood. Here, we report the critical role of early growth factor 4 (EGR4), a DNA-binding, zinc-finger transcription factor, in cell proliferation of SCLC. EGR4 overexpression in HEK293T cells conferred significant upregulation of specific splice variants of the parathyroid hormone-related protein (PTHrP) gene, resulting in enhancement of the secretion of PTHrP protein, a known mediator of osteolytic bone metastasis. More importantly, depletion of EGR4 expression by siRNA significantly suppressed growth of the SCLC cell lines, SBC-5, SBC-3 and NCI-H1048. On the other hand, introduction of EGR4 into NIH3T3 cells significantly enhanced cell growth. We identified four EGR4 target genes, SAMD5, RAB15, SYNPO and DLX5, which were the most significantly downregulated genes upon depletion of EGR4 expression in all of the SCLC cells examined, and demonstrated the direct recruitment of EGR4 to their promoters by ChIP and luciferase reporter analysis. Notably, knockdown of the expression of these genes by siRNA remarkably suppressed the growth of all the SCLC cells. Taken together, our findings suggest that EGR4 likely regulates the bone metastasis and proliferation of SCLC cells via transcriptional regulation of several target genes, and may therefore be a promising target for the development of anticancer drugs for SCLC patients.
The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p < 0.001), ileal isolation and anastomosis (73 min vs 45 min, p < 0.001), and stenting (23.0 min vs 6.5 min, p < 0.001). As the experience of the PSS increased, the time of the PSS procedures decreased.
Background: The flexible ureterorenoscope (URS) and associated devices have developed rapidly. However, despite its therapeutic benefits, URS may be associated with some complications. To the best of our knowledge, there are no studies discussing the complications of flexURS during the learning curve. Methods: A retrospective review of the records of patients who underwent flexURS from January 2005 to June 2013 was performed. To compare the complications after the introduction of flexURS, patients were divided into four groups based on the surgeon's training experience, that is, based on the number of cases performed by the surgeon. A total of 219 cases underwent flexURS. Groups 1, 2, 3, and 4 included 35, 50, 50, and 84 cases, respectively. The complications were classified using the Clavien system (I-IV). Results: The mean operation time and stone-free rate were significantly different (p < 0.001, p = 0.013, respectively). The total complication rates were 13.6, 10, 8.3, and 3.2%, respectively (p = 0.068). The more the surgeon's experience, the less was the complication rate. Despite our best efforts, the incidence of urosepsis was not reduced (p = 0.902). Conclusions: To reduce severe complications, it is necessary to have performed about 100 cases. Increased surgeon experience tended to decrease the risk of severe complications, but the incidence of urosepsis was not reduced.
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