Longitudinal Circulating Tumor DNA Modeling to Predict Disease Progression in First-Line Mutant Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer.

This exploratory, post hoc analysis aimed to model circulating tumor DNA (ctDNA) dynamics and predict disease progression in patients with treatment-naïve locally advanced/metastatic epidermal growth factor receptor mutation (EGFRm)-positive non-small cell lung cancer, from the FLAURA trial (NCT02296125). Patients were randomized 1:1 and received osimertinib 80 mg once daily (q.d.

Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion study.

Background: CNS metastases-including brain and leptomeningeal metastases-from epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) are associated with poor prognosis. AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier. We aimed to assess the safety, tolerability, pharmacokinetics, and efficacy of AZD3759 in patients with EGFR-mutant NSCLC with brain and leptomeningeal metastases.

Systemic administration of Abeta mAb reduces retinal deposition of Abeta and activated complement C3 in age-related macular degeneration mouse model.

Age-related macular degeneration (AMD) is a leading cause of legal blindness in the Western world. There are effective treatments for the vascular complications of neo-vascular AMD, but no effective therapies are available for the dry/atrophic form of the disease. A previously described transgenic CFH-gene deficient mouse model, (cfh-/-), shows hallmarks of early AMD.

Subcutaneously administered ofatumumab in rheumatoid arthritis: a phase I/II study of safety, tolerability, pharmacokinetics, and pharmacodynamics.

Objective: To investigate the safety and tolerability of a single subcutaneous (SC) dose of ofatumumab, a fully human anti-CD20 monoclonal antibody, in patients with rheumatoid arthritis (RA) taking background methotrexate (MTX). Secondary objectives included characterizing pharmacokinetics and pharmacodynamics.

Methods: In this single-blind, phase I/II study, 35 patients with RA were randomized in 5 cohorts to receive a single subcutaneous (SC) ofatumumab dose ranging from 0.

Dietary antioxidants decrease serum soluble adhesion molecule (sVCAM-1, sICAM-1) but not chemokine (JE/MCP-1, KC) concentrations, and reduce atherosclerosis in C57BL but not apoE*3 Leiden mice fed an atherogenic diet.

Dietary antioxidants are reported to suppress cellular expression of chemokines and adhesion molecules that recruit monocytes to the artery wall during atherosclerosis. In the present study we measured the effect of feeding apoE*3 Leiden mice or their non-transgenic (C57BL) littermates with atherogenic diets either deficient in, or supplemented with, dietary antioxidants (vitamin E, vitamin C and beta-carotene) for 12 weeks, on serum levels of CC (JE/MCP-1) and CXC (KC) chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1) and atherosclerotic lesion size. ApoE*3 Leiden mice developed gross hypercholesterolaemia, and markedly accelerated (10-20 fold; P < 0.

5-HT6 receptor antagonists improve performance in an attentional set shifting task in rats.

Rationale And Objective: Performance on the Wisconsin Card Sorting Test (WCST), which requires patients to 'shift attention' between stimulus dimensions (sorting categories), is impaired in diseases such as schizophrenia. The rat attentional set shifting task is an analogue of the WCST. Given that 5-HT(6) receptor antagonists improve cognitive performance and influence cortical neurochemistry in rats, the present study investigated the effects of 5-HT(6) receptor antagonists upon attentional set shifting in rats.

Short term arterial remodelling in the aortae of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging - implications for human pathology.

High-resolution, non-invasive imaging methods are required to monitor progression and regression of atherosclerotic plaques. We investigated the use of MRI to measure changes in plaque volume and vessel remodelling during progression and regression of atherosclerosis in New Zealand White rabbits. Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding.

Temporal relationships between circulating levels of CC and CXC chemokines and developing atherosclerosis in apolipoprotein E*3 Leiden mice.

Objective: CC and CXC chemokines are implicated in leukocyte recruitment during development of atherosclerotic lesions, suggesting circulating levels of chemokines may be useful serum markers of atherogenesis. Serum chemokine concentrations were measured in apolipoprotein (apo) E*3 Leiden mice and their nontransgenic littermates and related to the differing rates of atherogenesis in these animals.

Methods And Results: Mice were fed a high-fat, high-cholesterol/cholate (HFC/C) diet for 18 weeks.

Hypercholesterolaemia and circulating levels of CXC chemokines in apoE*3 Leiden mice.

Hyperlipidaemia may accelerate the development of atherosclerosis by enhancing the expression of chemokines by cells within the arterial wall. Chemokines of the CC subfamily are clearly implicated in atherogenesis; however, recent reports suggest that CXC chemokines may play a hitherto unrecognised role in monocyte recruitment into atheromatous lesions expressing these molecules. Here, we examine whether circulating levels of CXC chemokines may reflect the pathogenic changes occurring during early atherogenesis.