ABSTRACT
BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
Subject(s)
Animals , Mice , Humans , Proto-Oncogene Proteins c-akt/metabolism , Actins/metabolism , Neoplasm Recurrence, Local , TOR Serine-Threonine Kinases/metabolism , Urinary Bladder Neoplasms , Glycolysis , Cell Line, Tumor , Cell Proliferation , Mammals/metabolism , Tripartite Motif Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Integrin beta ChainsABSTRACT
The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).
ABSTRACT
The Chapter "Radical prostatectomy" has been completely update in the 2020 EAU prostate cancer guideline. Recommendation level of "No surgical approach has shown superiority in terms of functional or oncological results" and "Nerve-sparing surgery is not recommended when there is a risk of ipsilateral extracapsular extension" has been adjusted to "weak" . Various surgical techniques could further improve functional outcomes when performed appropriately based on the updated guideline.
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Objective To investigate the effect of pelvic floor stabilized structure preservation (PPSS) during robot-assisted laparoscopic radical prostatectomy (RARP)on postoperative continence recovery.Methods From October 2017 to April 2018,86 patients with prostatic cancer who underwent traditional RARP and RARP plus PPSS were included.There were 31 patients in non-PPSS group and 55 patients in PPSS group.In non-PPSS group,patients age was (68.48 ± 7.79) years old,BMI was (24.79 ± 3.05) kg/m2,median prostate volume was 63.54 (53.00-99.36) cm3,clinic T-stage T1-T2,T3,T4 accounted for 49.39％,22.58％,6.45％ and ISUP grade 1,2,3,4,5 accounted for 22.58％,22.81％,12.90％,12.90％,19.35％ respectively.In PPSS group,patients age was (69.53 ± 6.81)years old,BMI was (23.95 ± 3.03) kg/m2,median prostate volume was 73.39 (54.88-94.23) cm3,clinic T-stage T1-T2,T3,T4 accounted for 72.73％,7.27％,3.64％ and ISUP grade 1,2,3,4,5 accounted for 21.82％,18.18％,23.64％,18.18％,10.91％ respectively.The preoperative PSA,BMI,clinical T-stage,ISUP grade,and postoperative hospital days had no significant differences (P ＞ 0.05)between the two groups.Both groups were operated via transperitoneal approach.In the non PPSS group,endo-pelvic fascia and pubic prostate ligament was cut,and dorsal vessel complex was ligated.In PPSS group,the partial endo-pelvic fascia was bluntly pushed to the pelvic wall to preserve tendon arch,and pubic prostate ligament also was preserved without suturing and ligating dorsal vascular complex.The catheter was removed 7 d after RARP.The continence recovery were compared between the two groups,including pad number on the day of I,7,14,30,90 and ICI-Q-SF scores on the day of 30 and 90 after catheter removal.Results There was no significant difference in pad numbers used between the two groups on the day of 1,7,14,30 after catheter removal.On the 90th day,the proportions of using pad ≥4 in PPSS group were significantly lower than those in non-PPSS group (1.89％ vs.20.69％,P =0.004).No significant difference was found in ICI-Q-SF scores on the 30th and 90th day between the two groups.Univariate analysis showed that PPSS group used less pads than non-PPSS group on the 90th day [OR =0.07(95％ CI 0.01-0.65),P =0.019];T3 patients used more pads than T1-T2 patients [OR =9.19 (95％ CI 1.32-63.87),P =0.025].After adjusting for age,ISUP grading,T staging,and PSA,multivariate regression analysis showed that the risk of using pad ≥ 4 in PPSS group compared with non-PPSS group was 0.46,0.34,0.27,0.25,and 0.03 on the day of 1,7,14,30 and 90 after catheter removal,respectively.The PPSS approach didn't increase the risk of positive surgical margin.Conclusions Preservation of pelvic stabilized structure in RARP is very efficient in term of continence rate after RARP,and it does not increase the risk of positive surgical margin.
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Objective To illustrate the clinical and pathological features of Chinese upper tract urothelial carcinoma (UTUC) patients and to investigate the regional difference and the possible prognostic factors.Methods A retrospective study was performed on 2 628 patients from 9 centers of three different regions (Beijing:2 centers with 1 022 cases,Shanghai:1 center with 814 cases,Sichuan:6 center with 792 cases).The median age was 68 (range 20 to 93) and the mean age was 66.3.There were 1 447 male patients (55.1％) and 1 181 female patients (44.9％).The clinical information,pathological outcomes and prognosis were collected and analyzed based on South (Shanghai and Sichuan) and North (Beijing)region.Results The distribution of Ta + T1,T2,T3 and T4 was 914 (34.8％),715 (27.2％),857(32.6％) and 142(5.4％).Patients from North were more likely to be female (55.9％ vs.38.0％,P＜0.001) and suffer from ureteral tumors (43.4％ vs.35.9％,P ＜ 0.001);while in patients from South higher tumor stage(T3 or T4,42.5％ vs.31.0％,P ＜ 0.001),high grade(72.0％ vs.34.0％,P ＜0.001) and larger tumor size [(3.73 ±2.17) cm vs.(3.36 ±2.02) cm,P＜0.001] were more prevalent.Subgroup indicated that female patients in North had obviously lower tumor stage (T3 or T4,27.2％ vs.35.9％,P =0.014),while relatively higher tumor stage were noticed in female patients in South (T3 or T4,48.2％ vs.38.9％,P =0.004).The median follow-up was 41 (1-206) months,and 963 patients (36.6％) died including 815 (31.0％) died from cancer.In North female patients had better 5-year overall survival (75.5％ vs.62.2％,P ＜0.001) and cancer-specific survival (78.3％ vs.65.0％,P＜0.001),but in South gender had no impact on overall survival (58.5％ vs.60.1％,P =0.927) or cancer-specific survival (62.0％ vs.65.8％,P =0.345).Conclusions This study demonstrated that in Chinese patients with UTUC,those from North were featured for lower tumor stage and grade,higher proportion of females and females had better survival.High age,high tumor stage and grade,large tumor diameter,and the presence of lymph node metastasis or lymphovascular invasion were risk factors for poor prognosis in Chinese UTUC patients.