University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Deformability-based cell classification and enrichment using inertial microfluidics

Abstract: The ability to detect and isolate rare target cells from heterogeneous samples is in high demand in cell biology research, immunology, tissue engineering and medicine. Techniques allowing label-free cell enrichment or detection are especially important to reduce the complexity and costs towards clinical applications. Single-cell deformability has recently been recognized as a unique label-free biomarker for cell phenotype with implications for assessment of cancer invasiveness. Using a unique combination of fluid dynamic effects in a microfluidic system, we demonstrate high-throughput continuous label-free cell classification and enrichment based on cell size and deformability. The system takes advantage of a balance between deformability-induced and inertial lift forces as cells travel in a microchannel flow. Particles and droplets with varied elasticity and viscosity were found to have separate lateral dynamic equilibrium positions due to this balance of forces. We applied this system to successfully classify various cell types using cell size and deformability as distinguishing markers. Furthermore, using differences in dynamic equilibrium positions, we adapted the system to conduct passive, label-free and continuous cell enrichment based on these markers, enabling off-chip sample collection without significant gene expression changes. The presented method has practical potential for high-throughput deformability measurements and cost-effective cell separation to obtain viable target cells of interest in cancer research, immunology, and regenerative medicine.

Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy

Abstract: A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty-seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption.

Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab

Abstract: Cetuximab, an antibody directed against the epidermal growth factor receptor, is an effective clinical therapy for patients with colorectal, head and neck, and non–small cell lung cancer, particularly for those with KRAS and BRAF wild-type cancers. Treatment in all patients is limited eventually by the development of acquired resistance, but little is known about the underlying mechanism. Here, we show that activation of ERBB2 signaling in cell lines, either through ERBB2 amplification or through heregulin up-regulation, leads to persistent extracellular signal–regulated kinase 1/2 signaling and consequently to cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients who exhibit either de novo or acquired resistance to cetuximab-based therapy has ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximab, represent a rational therapeutic strategy that should be assessed in patients with cetuximab-resistant cancers.

A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure

Abstract: BackgroundContinuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. MethodsWe randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end poi...