Genomic Profiling of Metastatic Uveal Melanoma and Clinical Results of a Phase I Study of the Protein Kinase C Inhibitor AEB071.

Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed to evaluate the safety and efficacy of the orally available protein kinase C inhibitor, AEB071, in patients with metastatic UM, and to perform genomic profiling of metastatic tumor samples, with the aim to propose combination therapies. Patients with metastatic UM ( = 153) were treated with AEB071 in a phase I, single-arm study.

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

Background: Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity.

Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy.

Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-β, desmin, α-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31.

Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

Background: Immune response after viral infection usually involves T(H)1-mediated response; however, severe respiratory syncytial virus (RSV) infection appears to be associated with the development of asthma, a T(H)2-predominant phenotype.

Objective: To understand the early and subsequent immunologic response to a serious RSV infection in children over time.

Methods: A total of 206 previously healthy infants hospitalized with severe RSV bronchiolitis were enrolled in a prospective cohort called the RSV Bronchiolitis in Early Life study.

Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology.

Background: To prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients.

Methods: Using quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.

Elevated urinary leukotriene E4 levels are associated with hospitalization for pain in children with sickle cell disease.

Cysteinyl leukotrienes (CsyLTs) are inflammatory mediators produced by white blood cells. Leukotriene LTE(4) is the stable metabolite of CsyLTs, which can be measured in urine. We tested two hypotheses among children with sickle cell disease (SCD): (1) baseline urinary LTE(4) levels are elevated in children with SCD when compared with controls; and (2) baseline LTE(4) levels are associated with an increased incidence rate of hospitalization for SCD-related pain.

Epithelial cell proliferation contributes to airway remodeling in severe asthma.

Rationale: Despite long-term therapy with corticosteroids, patients with severe asthma develop irreversible airway obstruction.

Objectives: To evaluate if there are structural and functional differences in the airway epithelium in severe asthma associated with airway remodeling.

Methods: In bronchial biopsies from 21 normal subjects, 11 subjects with chronic bronchitis, 9 subjects with mild asthma, and 31 subjects with severe asthma, we evaluated epithelial cell morphology: epithelial thickness, lamina reticularis (LR) thickness, and epithelial desquamation.