Background Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. Methods RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. Results We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. Conclusions Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Background: Single-port robotic-assisted radical laparoscopic prostatectomy has emerged as a novel robotic-assisted radical laparoscopic prostatectomy in recent years, arousing wide attention. However, singleport robotic-assisted radical laparoscopic prostatectomy using Si da Vinci surgical system has been rarely reported, especially via the transperineal approach.Methods: We retrospectively collected 9 cases of prostate cancer patients who underwent transperineal single-port robot-assisted radical prostatectomy (t-spPARP) using Si da Vinci surgical system in our center from May 2020 to June 2020. The operation time, estimated blood loss (EBL), complications, changes in prostate-specific antigen (PSA) 3 months after surgery, and urinary continence recovery 6 months after surgery were analyzed.Results: No perioperative complications were recorded. The median [interquartile range (IQR)] operation time was 350 [150] min and the median [IQR] EBL was 300 [100] mL. PSA levels were less than 0.01 ng/mL at 3 months postoperatively in all cases (undetectable in 8 cases). All the 9 patients recovered their urinary continence 6 months after surgery and merely two patients required pads during the day.Conclusions: t-spRARP was verified as a safe and feasible surgical alternative to treat patients with localized prostate cancer, especially for those whose prostate is small-volume or who had abdominal surgery history.

Abstract:Objective: It is recommended that transurethral resection of the prostate (TURP) after brachytherapy should not be performed at an early stage after implantation. Herein we report our experiences and the results of channel TURP (cTURP) within six months post-implant for patients with refractory urinary retention. Methods: One hundred and ninety patients with localized prostate cancer of clinical stages T1c to T2c were treated by brachytherapy as monotherapy at our institution from February 2009 to July 2013. Nine patients who developed refractory urinary retention and underwent cTURP within six months after brachytherapy were retrospectively reviewed and analyzed. Results: The median interval between prostate brachytherapy and cTURP was three months (range 1.5 to 5.0 months). There were no intraoperative or postoperative complications and no incontinence resulting from the surgery. All urinary retention was relieved per the American Brachytherapy Society urinary symptom score. With a mean follow-up time of 16 months (range 6 to 26 months) after cTURP, no patient experienced biochemical recurrence. The mean serum prostate-specific antigen (PSA) of the patients who underwent cTURP was 0.42 ng/ml (range 0.08 to 0.83 ng/ml) at the end of their follow-up. Conclusions: Early cTURP was found to be safe and effective in relieving urinary retention after brachytherapy and could be performed without compromising its therapeutic efficacy.