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.

HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the EGF receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTKs) in glioblastoma (GBM). While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate GBM in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival, suggesting that HBEGF may be a clinically relevant target.

Analysis of fusion gene expression in prostate tumors by using single-end reads.

Fusion gene expression, a kind of chromosome rearrangement mode, has been strongly linked to prostate cancer diagnosis and prognosis as well as to the Gleason score and the American Joint Committee on Cancer stage assessment. In combination with traditional methods for locating fusion genes and scoring their association with cancer cell growth, proliferation, and invasion through the basement membrane, the emerging high-throughput sequencing technologies offer a panorama of fusion genes in a genome and facilitate the discovery of new fusion modes. We describe here a method for using single-end reads to analyze fusion gene expression in prostate tumors. We obtained the fusion gene expression profiling of prostate tumors, clustered them into several biological pathways, highlighted three "rediscovered" fusion genes (TMPRSS2-ERG, KLK2, and KLK3) and proved the reliability of our method.

Erythrocyte trans-fatty acids, type 2 diabetes and cardiovascular risk factors in middle-aged and older Chinese individuals.

AIMS/HYPOTHESIS: Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2 diabetes and cardiovascular risk factors in Chinese individuals. METHODS: Erythrocyte fatty acids were measured by gas chromatography among 3,107 men and women (50-70 years) recruited from urban and rural areas in Beijing and Shanghai, China. RESULTS: Total trans-18:1 and two trans-18:2 isomers were detected and accounted for 0.37% of the total fatty acids in the erythrocytes. Concentrations of TFAs were higher in women than men, and in urban than rural residents. Of the TFAs, trans-18:1, but not trans-18:2, showed a modest association with dairy consumption (ß = 0.27), but not with other foods. After adjustment for BMI, social-demographic, lifestyle and dietary factors and other TFAs, erythrocyte trans-18:1 was shown to be associated with a lower risk of type 2 diabetes (OR comparing extreme [first and fourth] quartiles 0.68, 95% CI 0.48, 0.97, p(trend) = 0.02), as well as 20-50% lower odds of central obesity, dyslipidaemia, hyperglycaemia, insulin resistance and chronic inflammation. In contrast, trans-18:2 fatty acids were positively associated with high triacylglycerol (p(trend) < 0.001) and LDL-cholesterol (p(trend) = 0.03) levels, but not with diabetes and other cardiometabolic risk factors. CONCLUSIONS/INTERPRETATION: Among middle-aged and older Chinese individuals with overall low erythrocyte TFAs levels, trans-18:1 might serve as a marker of dairy intake. Higher trans-18:1 levels were associated with a lower risk of type 2 diabetes, whereas higher trans-18:2 levels were associated with dyslipidaemia.

Hepatitis C virus infection: its role in chronic liver diseases.

In order to find out the infectious rate of hepatitis C virus (HCV) among chronic liver diseases, we investigated antibodies against hepatitis C virus and HCVRNA by method of ELISA, RIBA and RT-PCR in 410 patients with chronic liver disease. The prevalence of HCV infection was found to be 4%. Whereas the positive rate of HBsAg and HBV-DNA of these cases was 69% and 58%, respectively. There is no statistical significance between HCV infectious rate of patients with positive and negative HBsAg. The relative low infectious rate of HCV infection among chronic hepatic diseases indicates that HBV infection plays a more important role in causing chronic hepatitis than that of HCV. Thus, special emphasis should be paid to the preventive and therapeutic measures against hepatitis B in China.

[Combination of phentolamine and angelicini in cholestasis and severe type of chronic active hepatitis B].

Among 60 patients with chronic active hepatitis B, 43 were of the severe type, 17 were of cholestasis type. Each type was divided randomly into two groups: therapeutic and control. The former received both conventional supporting therapy and combination of phentolamine (20-30 mg/day) and angelicini (150-450 mg/day). The latter was only treated with conventional supporting therapy. Digital subtraction angiography (DSA) and platelet agglutination test were performed in 10 patients respectively. DSA demonstrated that liver sinusoids were expanded and the vascular bed round the sinusoids were also enlarged in diameter following instillation of phentolamine. It was also shown that angelicini could suppress the second phase of platelet agglutination. These indicated that phentolamine and angelicini could improve the liver microcirculation in different way. The incidence of survival between therapeutic and the control group was 57.14% and 31.82% respectively (P less than 0.05).

Optical fibers for measurement of earth strain.

We report on laboratory experiments on single-mode optical fibers for use in measuring earth strain. We have monitored the long-term stability of 25-m long tensioned fibers and found their rates of fractional change in optical path lengths to be no more than 2 x 10(-6)/yr. The optical temperature coefficients for several fibers whose physical lengths were held constant were found to be within 4% of 1.17 x 10(-5) apparent strain/ degrees C. The strain sensitivity (the ratio of observed optical path change to physical path change) was determined to be within 1% of 1.16 for all the fibers tested. Initial field tests indicate that fibers are suitable for earth strain measurements of moderate precision.