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.

Exit-wave phase retrieval from a single high-resolution transmission electron microscopy image of a weak-phase object.

We propose a novel algorithm to numerically retrieve the phase of the exit-wave function from a high-resolution transmission electron microscopy (HRTEM) image of a weak-phase object material, e.g., graphene and hexagonal boron nitride monolayers. It theoretically only requires a single HRTEM image to retrieve the phase under the assumption of a weak-phase object. In addition, it can remove the effects of geometrical aberrations up to fifth order, and also improve the degraded information due to the finite temporal and spatial coherence. We further present its applications and successfully demonstrate the identification of the lattice atoms and line defects in single HRTEM image of graphene.

Multiple-ellipse fitting method to precisely measure the positions of atomic columns in a transmission electron microscope image.

In this paper, we propose a multiple-ellipse fitting method to accurately determine the atomic column positions in transmission electron microscopy (TEM) images. The column is enclosed by a series of ellipses fitted from contour lines at equidistant intensity levels, and each atomic column is shaped by an averaged elliptical shape to obtain its positions. In particular, the intensity profile of the atomic column can be obtained by an elliptically rotational average based on its shape; therefore, the intensities of the neighbouring atomic column can be subtracted for each atomic column during subsequent position refinement. This method can achieve precision in the picometre range, and we quantitatively measure this precision by analysing an image containing two Gaussian-shaped atoms and some simulated high-resolution transmission electron microscopy (HRTEM) images of SrTiO3.

[A case-control study on the association between serum lipid level and the risk of breast cancer].

Objective: To examine the association between serum lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the risk and progression of breast cancer in postmenopausal and premenopausal women. Methods: A review analysis of female patients who underwent breast cancer surgery and blood lipid metabolism testing in Tianjin One Hospital, from January 2013 to October 2013, was performed. A total of 1 081 patients were included in the final analysis. The control group consisted of 2 981 women without breast cancer. We collected all of the cases' demographic, pathology, lymph nodes metastasis information, was used to testify the difference of serum lipid level between patient and control group, also the postmenopausal and pre-menopausal groups. Results: The average age of the patients and control subjects were (51.6±0.3) and (51.0±0.2) years, respectively. Serum TC and LDL-C levels in the patient group, (5.16± 0.03) and (3.28±0.26) mmol/L, respectively, were significantly higher than in the control group, (5.02±0.01) and (2.51 ± 0.01) mmol/L, respectively (t values 3.89 and 4.81 and P<0.001). HDL-C levels in the patient group, (1.60±0.01) mmol/L, were significantly lower than in the control group, (1.65±0.01) mmol/L (t=3.90, P<0.001). Similar observations were made in postmenopausal patients. Serum TC and LDL-C levels in the postmenopausal patient group, (5.48±0.04) and (3.27±0.03) mmol/L, respectively, were significantly higher than in control subjects, (5.24±0.02) and (2.71±0.02) mmol/L, respectively (t values 4.75 and 15.30, all P values <0.001). HDL-C levels in postmenopausal patients, (1.60±0.02) mmol/L, were significantly lower than in the control group, (1.69±0.01) mmol/L (t=4.85 , P<0.001). In the breast cancer patient group, those at pathological stages 0-Ⅱ had lower TG levels than those at Ⅲ-Ⅳ. These values were (1.19±0.05) and (1.43± 0.09) mmol/L, respectively (t=2.69, P<0.001). Meanwhile, patients with no lymph node metastases had lower TG levels than the lymph node-positive group, with values of (1.15 ± 0.05) and (1.37 ± 0.07) mmol/L, respectively (t=2.53, P=0.012). Conclusion: We found that dyslipidemia may affect the incidence of breast cancer, particularly among postmenopausal women. Serum lipids may promote cancer progression through higher TG and low HDL-C levels.

Aurora-A is a determinant of tamoxifen sensitivity through phosphorylation of ERα in breast cancer.

Despite the clinical success of tamoxifen, its resistance remains a major challenge in breast cancer. Here we show that Aurora-A determines tamoxifen sensitivity by regulation of oestrogen receptor (ER)α. Ectopic expression of Aurora-A decreases and depletion of Aurora-A enhances tamoxifen sensitivity in ERα-positive breast cancer. Elevated Aurora-A was significantly associated with the recurrence of ERα-positive tumours. Notably, Aurora-A inhibitor MLN8237, which is currently in clinical trial, synergizes with tamoxifen and overcomes tamoxifen resistance. Furthermore, Aurora-A interacts with and phosphorylates ERα on serine-167 and -305, leading to increase in ERα DNA-binding and transcriptional activity. Elevated levels of Aurora-A are significantly associated with disease-free survival in ERα-positive but not ERα-negative breast cancers. These data suggest that Aurora-A has a pivotal role in tamoxifen resistance and ERα is a bona fide substrate of Aurora-A. Thus, Aurora-A represents a prognostic marker in ERα-positive tumour and a critical therapeutic target in tamoxifen-resistant breast cancer, and Aurora-A inhibitor could be used as either an independent or concurrent agent in tamoxifen-resistant tumour.

[CT studies on obstructive sleep apnea syndrome].

To ascertain whether there are structural and functional changes in the upper airway of obstructive sleep apnea syndrome (OSAS) pts. We studied 33 pts of OSAS with positive polysomnographic tests, 14 pts of non-apnea snore with negative polysomnographic tests, and 18 normal subject by using CT scanner (Somatom Dr 3). The results are as followings 1. There were narrowing region in the upper airway in OSAS pts and the non-apnea snore pts. Most of the narrowings were located at the level of oropharynx, which was correspondent to the level of the soft palate and the uvula. The length of the soft palate and the pre-spinal soft tissue thickness of two groups of pts were larger than non-snore individual. 2. The pharyngeal compliance was significantly higher in OSAS pts than in non-apnea snore pts. 3. There was no localised deposition of fat tissue surrounding the lumen of upper airway. 4. CT scanning is the non-invasive and more useful procedure for the diagnosis of OSAS and also would help to select the pts for surgery.