Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours

BACKGROUND: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers. METHODS: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD. RESULTS: Study 1280.1 involved 61 patients (part I: xentuzumab 10–1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10–3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD. CONCLUSIONS: Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity

Development of Microwave Filters with Tunable Frequency and Flexibility Using Carbon Nanotube Paper

This study aims to exploit the distinctive properties of carbon nanotube materials, which are particularly pronounced at the microscopic scale, by deploying fabrication techniques that allow their features to be observed macroscopically. Specifically, we aim to create a semiconductor device that exhibits flexibility and the ability to modulate its electromagnetic wave absorption frequency by means of biasing. Initially, we fabricate a sheet of carbon nanotubes through a vacuum filtration process. Subsequently, phosphorus and boron elements are separately doped into the nanotube sheet, enabling it to embody the characteristics of a PN diode. Measurements indicate that, in addition to the fundamental diode’s current–voltage relationship, the device also demonstrates intriguing transmission properties under the TEM mode of electromagnetic waves. It exhibits a frequency shift of approximately 2.3125 GHz for each volt of bias change. The final result is a lightweight and flexible carbon-based semiconductor microwave filter, which can conform to curved surfaces. This feat underscores the potential of such materials for innovative and effective electromagnetic wave manipulation

Treatment of infective endocarditis caused by methicillin-resistant Staphylococcus aureus: teicoplanin versus vancomycin in a retrospective study.

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) is increasing. Vancomycin and teicoplanin are 2 intravenous glycopeptides appropriate for its treatment. There is no human study comparing teicoplanin and vancomycin for the treatment of MRSA endocarditis. Between 1996 and 2006, 51 MRSA endocarditis patients were treated at the authors' hospital. There were 29 patients with nosocomial infection; 15 were treated with teicoplanin. Teicoplanin was used as the first therapeutic agent in 3 patients because of renal insufficiency. Vancomycin was used as the first therapeutic agent in 12 patients. Treatment was changed to teicoplanin because of adverse reactions in 10 and persistent bacteremia in 2 patients. Early operation was performed in 2 patients because of persistent MRSA bacteremia. Overall, 7 patients died in hospital. There was no statistically significant difference in hospital mortality rate (42% vs 47%) and bacteriologic failure rate ( 34% vs 40%) between 36 patients treated with vancomycin and 15 patients treated with teicoplanin. Teicoplanin can be an alternative therapy of MRSA infective endocarditis