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.

FOSL1 enhances growth and metastasis of human prostate cancer cells through epithelial mesenchymal transition pathway.

OBJECTIVE: To investigate the effect of highly-expressed FOSL1 on the tumorigenesis and metastasis of prostate cancer. PATIENTS AND METHODS: Researches were carried out in human prostate cancer tissues and cell lines. In prostate cancer tissues, the expression of FOSL was detected by immunohistochemistry. In vitro cell line experiments, we constructed a prostate cancer cell model with FOSL1 stable knockdown and tested cell proliferation and metastasis before and after knockdown of FOSL1. Finally, the epithelial-mesenchymal transition (EMT) markers before and after interference of FOSL1 were also analyzed. RESULTS: FOSL1 was confirmed to have a high expression in prostate cancer. Transwell experiments demonstrated that FOSL1 could enhance prostate cancer metastasis, while in vivo experiments revealed an accelerated progression of prostate cancer caused by FOSL1. In addition, Western blot analysis revealed an elevated level of N-cadherin and Snail1 and a reduced level of E-cadherin that was induced by FOSL1. CONCLUSIONS: FOSL1 can promote the occurrence and progression of prostate cancer by altering the EMT process of cells.

Effects of paclitaxel combined with miR-448 on growth and proliferation of bladder cancer EJ cells.

OBJECTIVE: Bladder cancer is one of the most common malignant tumors of the urinary system characterized by a high recurrence rate after treatment. Paclitaxel is a new type of anti-neoplastic agent used for treatment by inhibiting the proliferation of bladder cancer cells. This study aimed to explore the mechanism of paclitaxel on the inhibition of bladder cancer cell proliferation by applying paclitaxel combined with miR-448 on bladder cancer cells. MATERIALS AND METHODS: Bladder cancer EJ cells were divided into 5 groups, including control group, paclitaxel group, negative control (NC) group, microRNA-448 (miR-448) mimic group, and paclitaxel combined with miR-448 mimic group. Cell apoptosis was tested by flow cytometry. Cell proliferation was determined by cell counting kit 8 (CCK8) assay. The regulation of miR-448 on B cell lymphoma 2 (Bcl-2) gene was assessed by dual luciferase reporter assay. Bcl-2 protein expression was detected by Western blot. RESULTS: The apoptotic rate of cells was significantly increased, while the cell proliferation ability was significantly reduced in paclitaxel group and miR-448 mimic group compared with control (p<0.05). Cell apoptotic rate in paclitaxel combined with miR-448 mimic group was markedly higher than that of paclitaxel group (p<0.05). MiR-448 can bind to the 3'UTR region of Bcl-2 mRNA and regulate the expression of Bcl-2. The expression of Bcl-2 protein in paclitaxel group and miR-448 mimic group was significantly lower than that in control group and higher than paclitaxel combined with miR-448 mimic group (p<0.05). CONCLUSIONS: Paclitaxel combined with miR-448 promoted EJ cell apoptosis and inhibited cell proliferation by suppressing Bcl-2 gene expression.

Meta-analysis of the relationship between slow acetylation of N-acetyl transferase 2 and the risk of bladder cancer.

The incidence of bladder cancer is closely associated with exposure to aromatic amines, that can cause cancer only after metabolic activation regulated by N-acetyl transferase 1 and 2 (NAT1 and NAT2). Many studies have indicated that slow acetylation of NAT2 increases the risk of bladder cancer. The major risk factor is tobacco smoke; however, some studies have failed to prove this. This study attempted to explore the correlation between NAT2 slow acetylation and bladder cancer risk through a meta-analysis of published case-control studies. Studies detecting NAT2 gene status in bladder cancer patients and healthy controls were retrieved from PubMed, Cochrane, EMchrane, CBM, and CNKI. We retrieved the data of cited articles and publications to identify and compare NAT2 gene in bladder cancer patients and healthy controls. The variables within and between the studies were also considered. The META module in the Stata v.6.0 software was used for data analysis. Twenty independent studies were enrolled in our meta-analysis according to the inclusion and exclusion criteria. Individual differences in the bladder cancer susceptibility were, in part, attributed to the effect of carcinogens. The merged odds ratio of the effect of slow acetylation on bladder cancer was 1.31 (95% confidence interval = 1.11-1.55). In conclusion, NAT2 slow acetylation state was associated with bladder cancer risk, and was shown to modestly increase the risk of bladder cancer.