No abstract

Ubiquitination is a critical biological process in post-translational modification of proteins and involves multiple signaling pathways in protein metabolism, apoptosis, DNA damage, cell-cycle progression, and cancer development. Deubiquitinase, a specific enzyme that regulates the ubiquitination process, is also thought to be closely associated with the development and progression of various cancers. In this article, we systematically review the emerging role of the deubiquitinase ubiquitin-specific peptidase 11 (USP11) in many cancer-related pathways. The results show that USP11 promotes or inhibits the progression and chemoresistance of different cancers, including colorectal, breast, ovarian, and hepatocellular carcinomas, via deubiquitinating several critical proteins of cancer-related pathways. We initially summarize the role of USP11 in different cancers and further discuss the possibility of USP11 as a therapeutic strategy.

No abstract

4507 Background: Pts with multiple or tumors with large invasion areas which are un-completely-resectable through TURBT would be recommended radical cystectomy in the clinical treatment. The KEYNOTE-057 study has illuminated the efficiency of immune checkpoint inhibitors monotherapy in HR-NMIBC pts, with acceptable adverse events (AEs). However, the role of PD-1/PD-L1 inhibitor in combination with chemotherapy in NMIBC pts remains unclear. We report preliminary treatment efficiency, safety data, and exploratory work of TRUCE-02 trial. Methods: TRUCE-02 is a phase II study for NMIBC pts with uncompletely resectable tumour by TURBT. The primary endpoint was complete response(absence of non-muscle-invasive bladder cancer or progressive disease). Pts that meet the criteria would receive tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 or 4 cycles followed by a comprehensive assessment including pathology, urine cytology, and imageology. Meanwhile, biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay) and whole transcriptome RNA sequencing of the tumor. Results: Between July 2020 and January 2022, 54 pts were enrolled. 42 pts have completed whole 3 or 4 treatment cycles and reached the primary endpoint. 23 pts achieved CR condition (56%, 95%CI, 43.6% and 74.4%). ORR of 60% (N=25/42, 95%CI, 45.2% and 74.8%). As a secondary endpoint, 33 pts remain cystectomy-free condition (78.6%, 95%CI, 66.2% and 91%). Grade 3-4 AEs were lower than 2%. Urine cytology showed its diagnostic efficiency of 68.42% (95%CI, 61.3% and 75.6%), urine FISH showed a diagnostic efficiency of 45.71% (95%CI, 37.7% and 53.4%) before pathological assessment. As for PD-L1 expression, 47.3% (N = 9/19) of response pts (CR+PR) showed positive, 50% (N = 5/10) of un-response pts (PD+SD) showed positive. We also found out through sequencing results that AR, TCF7L2 might be underlying markers that predict adverse outcomes for pts in this crew. HRR mutation may predict a positive prognosis and mutations in NMIBC which might predict the prognosis of this treatment plan. Conclusions: Tislelizumab with nab-paclitaxel represents a novel treatment option with a satisfactory benefit in treating NMIBC. PD-L1 expression has no obvious correlation with the efficiency of this treatment plan. WGS result also showed that there are mutation markers that may predict whether pts would benefit from this treatment plan. Clinical trial information: NCT04730232. [Table: see text]

Introduction The effect of repeated cystoscopy on bladder cancer (BC) patient anxiety and feelings is rarely evaluated. Aim To compare the difference of patients’ anxiety and subjective feelings caused by different cystoscopes. Material and methods We prospectively included 192 BC patients who accepted regular cystoscopy follow-up after transurethral resection of bladder tumor (TURBT): 93 in the flexible group and 99 in the rigid group. The method of anesthesia and the order of examinations were consistent between different groups. We analyzed the anxiety level before cystoscopy, the maximum pain during the examination and the change of lower urinary tract symptoms (LUTS) before and after cystoscopy. Meanwhile, we analyzed the rate of gross hematuria and pyuria after cystoscopy. The anxiety and pain levels were evaluated by the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and visual analogue scale (VAS). LUTS was reflected by the Core Lower Urinary Tract Symptom Score (CLSS). We distinguished gender during analysis. Results The median APAIS score of male patients undergoing flexible or rigid cystoscopy was 8 vs. 12 (p < 0.01), and this result for females was 8 vs. 9 (p = 0.048). The median pain scores for men in the two groups was 1 vs. 2 (p < 0.01), respectively, and this outcome in female patients was 0 vs. 1 (p < 0.01). Patients in the rigid group had more CLSS change (0 vs. 1, p < 0.01). There was no difference in pyuria or gross hematuria rate after examination. Analysis in respective groups showed that men have more severe pain than women, 1 vs. 0 (p = 0.001) in the flexible group and 2 vs. 1 (p = 0.009) in the rigid group. Conclusions A flexible cystoscope can improve anxiety and subjective feelings of BC patients during cystoscopy follow-up.