Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Application of Endo-GIA stapler in laparoscopic radicalcystectomy].

Objective: To explore the application of Endo-GIA stapler in laparoscopic radical cystectomy, especially in the treatment of lateral bladder ligament, and to evaluate its clinical feasibility and practicability. Methods: A retrospective analysis of clinical data about 38 cases of laparoscopic radical cystectomy (LRC) treated in the Department of Urology, Chaoyang Hospital of Beijing and Cancer Hospital, Chinese Academy of Medical Sciences from July 2017 to June 2019 were conducted. The patients were divided into Endo-GIA stopler group(18 cases) and non-Endo-GIA stopler group (20 cases) according to whether Endo-GIA stapler were used. The basic clinical data, operation time of bladder lateral ligament, operation time of bladder lateral wall, operation time of bladder resection, amount of bleeding during operation, pathological data after operation and related indicators of recovery after operation were compared between the two groups. Results: All 38 patients underwent radical cystectomy (RC) successfully under 3-D laparoscopy without conversion to open surgery. The operation time of bladder lateral ligament in Endo-GIA stapler group was significantly shorter than that in non-Endo-GIA stapler group [(3.25±0.75) min vs (9.20±2.95) min, P=0.042]; the operation time of bladder lateral wall in Endo-GIA stapler group was significantly shorter than that in non-Endo-GIA stapler group [(8.06±1.66) min vs (14.30±3.37) min, P=0.016]. The operation time of cystectomy in the Endo-GIA stapler group was significantly shorter than that in the non-Endo-GIA stapler group [(47.06±4.70) min vs (61.60±14.91) min,P=0.003]. The amount of bleeding in the Endo-GIA stapler group was significantly shorter than that in the non-Endo-GIA stapler group [(37.77±21.30) ml vs (114.50±39.80) ml, P=0.015]. The time of drainage tube removal in Endo-GIA group was significantly shorter than that in the non-Endo-GIA group [(5.83±1.54) d vs (7.30±3.00) d, P=0.002]. The length of post-hospitalization in Endo-GIA group was significantly shorter than that in the non-Endo-GIA group [(7.67±1.78) d vs (9.60±3.25) d,P=0.036]. However, there was no significant difference in other basic clinical data, post-operative pathology and post-operative recovery related indicators. Conclusions: Laparoscopic radical cystectomy using Endo-GIA stapler device is safe and feasible. It is easy to operate, shorten the operation time significantly, and reduce the amount of bleeding. To a certain extent, it is conducive to the recovery of patients after operation to some extent, and worthy of clinical application.

DANCR sponges miR-135a to regulate paclitaxel sensitivity in prostate cancer.

OBJECTIVE: Paclitaxel is one of the most common drugs for cancer treatment. LncRNA DANCR is a regulator of up-regulation in tumors. Our experiment aims to clarify the role of DANCR in paclitaxel sensitivity of prostate cancer. PATIENTS AND METHODS: We found that the expression of DANCR in prostate cancer tissues and cells was significantly higher than that in normal groups. DANCR knockdown could reduce cell proliferation and induce cell apoptosis in cells. Moreover, DANCR silence enhanced the effect of paclitaxel on cell proliferation and apoptosis in prostate cancer cells. RESULTS: DANCR targeted and negatively regulated the expression of miR-135a. miR-135a overexpression inhibited cell proliferation and promoted cell apoptosis and paclitaxel sensitivity in prostate cancer cells. miR-135a inhibition reversed the promoting effect of DANCR silence on paclitaxel sensitivity in prostate cancer cells. CONCLUSIONS: Downregulation of DANCR increased paclitaxel sensitivity in prostate cancer cells by negatively regulating the expression of miR-135a.

A multi-center, controlled, randomized, open-label clinical study of levofloxacin for preventing infection during the perioperative period of ultrasound-guided transrectal prostate biopsy.

By comparing the safety and efficacy of 500 mg of oral levofloxacin for 3 days with those of intravenous antibiotics for 3 days in the prevention of infectious complications of ultrasound-guided transrectal prostate biopsy (TPB), we provided a safe and cost-effective infection preventive protocol for TPB in China. A total of 801 patients with indications for TPB in 12 centers were randomized into two groups from October 2011 to December 2015. Patients in the test group (n = 392) took 500 mg of oral levofloxacin for 3 days. Patients in the control group (n = 409) underwent intravenous antibiotics according to the traditional habits of the center for 3 days. All patients underwent ultrasound-guided TPB. Infectious complications were compared between the two groups. Different kinds of antibiotic were used in the control group. Comparing the two groups, the mean patient age was 70.6 ± 14.0 and 70.5 ± 14.0 years. The incidence of total infectious complications was 4.6 % (18/392) and 4.4 % (18/409) respectively, the incidence of asymptomatic bacteriuria was 3.1 % (12/392) and 2.7 % (11/409), the incidence of symptomatic urinary tract infection was 0.0 % and 0.2 % (1/409), the incidence of fever was 0.8 % (3/392) and 0.5 % (2/409), the incidence of bacteremia was 0.5 % (2/392) and 0.0 %, and the incidence of urosepsis was 0.3 % (1/392) and 1.0 % (4/409) respectively (all P > 0.05). The selection of antibacterial agents for TPB is in ca haotic condition in China. Oral levofloxacin at 500 mg once daily for 3 days is a safe, convenient, and cost-effective infection preventive protocol for TPB in China.

Testicular hypofunction caused by activating p53 expression induced by reactive oxygen species in varicocele rats.

We investigated the mechanism of the testicular hypofunction induced by hypoxia in varicocele rats. Varicocele was induced by partial ligation of the left renal vein. Seven weeks later, left testis mass index was measured. The sperm counts and motility were tested by CASA. The change of seminiferous tubule tissue was observed by HE staining. The reactive oxygen species (ROS) level in left testicular tissue was measured by ELISA, and the expressions of HIF-1α and p53 were detected by immunohistochemistry and Western blot. The left testis mass index and the sperm motility were significantly lower in surgery group. By HE staining, the left seminiferous epithelial cell arrangement was incompact, disordered and vacuolated in surgery group. The ROS level in surgery group was significantly higher than the other groups. The results of immunohistochemistry and Western blot indicated that the expressions of HIF-1α and p53 increased significantly in surgery group. Our study demonstrated that varicocele caused hypoxia that could cause the rise of ROS level to induce the increase of p53 expression, leading to the decrease of testis mass index and changes of seminiferous tubules, which would reduce sperm motility and result in male infertility eventually.

Expression profiles of variation integration genes in bladder urothelial carcinoma.

Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

Y-27632 improves the erectile dysfunction with ageing in SD rats through adjusting the imbalance between nNo and the Rho-kinase pathways.

We investigated whether the effect of Y-27632 to improve the erectile function in SD rats was associated with the degree of the imbalance between nNOS and the Rho-kinase pathways. Western blot analysis was used to evaluate nNOS and Rho-kinase protein expression in 10 young and 10 old SD rats. Imbalance value between nNOS and Rho-kinase protein levels was obtained by subtracting nNOS from Rho-kinase. A 5-V stimulus was given in SD rats before and after the administration of 200 nmol kg(-1) of Y-27632 intracavernosally and ICP/MAP was recorded. The improvement of erectile function induced by Y-27632 was expressed as the margin of ICP/MAP after and before the administration of Y-27632. In young rat group, the contents of nNOS and Rho-kinase protein were 1.7 +/- 0.15 and 1.8 +/- 0.14 respectively. In old rat group, the nNOS protein decreased to 1 +/- 0.15, and in contrast, the Rho-kinase protein increased to 2.6 +/- 0.2. The imbalance value between nNOS and Rho-kinase was 0.2986 +/- 0.1109 and 1.5961 +/- 0.1206 in young and old rat groups. The improvement of erectile function induced by Y-27632 was 0.0500 +/- 0.0294 and 0.3420 +/- 0.660 in young and old rat groups. In all rats, the correlation coefficient between the imbalance value of nNOS and Rho-kinase and the improvement of erectile function was 0.649, P < 0.01. In conclusion, this study suggested that impaired erectile function with ageing in SD rats be associated with the imbalance between nNO and Rho-kinase activity and Y-27632 could improve the erectile function in old SD rats through adjusting this imbalance.