D. Ye

Germline mutations of renal tumor predisposition genes in early-onset patients

Junlong Wu1,2,#, Hongkai Wang1,2,#, Christopher J. Ricketts3,#, Youfeng Yang3, Chengyuan Gu1,2, Maria J. Merino3, Hailiang Zhang1,2, Guohai Shi1,2, Hualei Gan2,4, W. Marston Linehan3,*, Yao Zhu1,2,*, Dingwei Ye1,2,* 1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3. Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

UHRF1BP1: A tumor suppressor gene associated with bladder cancer risk in Han Chinese

Junlong Wu1, Yao Zhu1, Dingwei Ye1, Meilin Wang3, Jianfeng Xu3, Chengyuan Gu1, Weijie Gu1 1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China 2. Department of Genetic Toxicology, the key laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China 3. Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China

Axitinib Versus Placebo as an Adjuvant Treatment for Renal Cell Carcinoma: Results From the Phase III, Randomized ATLAS Trial

Abstract Background The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660–1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468–0.879; P = 0.0051), and by IRC (0.735; 0.525–1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number NCT01599754

Expression of OPN in rat kidney with different doses of vitamin K 3 injection

Osteopontin (OPN) is a phosphorylated glycoprotein that occurs in high levels in bone, but is also present at sites of pathological calcification. Based on autotitration, OPN is regarded as a potent inhibitor of hydroxyapatite crystal formation, an activity that requires phosphorylation of the protein. Vitamin K is also a stone inhibitor, which has an effect on vitamin K-dependent gamma-glutamyl carboxylase activity. To explore the mechanism, using different doses of vitamin-K, we developed an enzyme-linked immunosorbent assay (ELISA) using a combination of mouse monoclonal antibodies against OPN in the rat kidney. We also investigated the expression of OPN mRNA in the kidney in an experimental model of a renal stone, using mass spectrometry to identify 27 serines and two threonines that are phosphorylated in the stone isoform of OPN.