Sonya Cressman

Synthesis of a Labeled RGD-Lipid, Its Incorporation into Liposomal Nanoparticles, and Their Trafficking in Cultured Endothelial Cells

The use of targeting ligands to enhance the delivery of liposomal nanoparticles (LNs) has moved slowly toward clinical application. This relative lack of clinical progression is further complicated by the existence of conflicting in vivo results in the literature. In this work, we describe new formulations of LNs that are targeted with an arginine-glycine-aspartic acid-containing peptide, cRGDfK, conjugated to the lipid distearoyl phosphatidylethanolamine (DSPE). These formulations may be able to circumvent some of the challenges encountered during the development of targeted-LNs. Of the constructs studied, a fluorescently labeled peptide-lipid conjugate was incorporated into LNs with high yield and accuracy. It is shown that the resulting targeted-LNs bind to human umbilical vein endothelial cells (HUVECs) with increasing avidity as the amount of peptide displayed on the LN surface increases. We specifically demonstrate the ability of targeted-LNs loaded with doxorubicin and incubated with HUVECs to deliver the drug to the cytosol. The cell does not internalize nontargeted LNs, supporting the notion that the RGD motif is associated with internalization of the targeted LN.

Capillary Electrophoresis Frontal Analysis for Characterization of αvβ3 Integrin Binding Interactions

The specific binding characteristics of alphavbeta3 integrins with an arginine-glycine-aspartic-acid (RGD) containing fluorescently labeled cyclic peptide is investigated with capillary electrophoresis-frontal analysis method. The new algorithm used to calculate the binding constants and binding stoichiometry was derived without the assumptions made in the commonly used Scatchard Plot method, thus enabling the determination of specific binding parameters in the presence of nonspecific binding. The alphavbeta3 integrin, a membrane protein, was studied in solution, without the need of immobilization or any other kind of modification. An RGD containing fluorescently labeled cyclic pentapeptide is used as the ligand with both specific and nonspecific binding characteristics, and an arginine-alanine-aspartic-acid (RAD) containing peptide is used as the control for nonspecific binding. While a typical specific binding isotherm has a shape of a rectangular hyperbola, a nonspecific binding isotherm is linear in the same ligand concentration region. A 1:2 specific binding stoichiometry was revealed with the second binding having a similar affinity compared to the first binding event.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer’s perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. Results: The average per-person cost for screening individuals with LDCT was

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency

453 (95% confidence interval [CI],

A Time-Trend Economic Analysis of Cancer Drug Trials

400–

Nonmedical Costs in Patients Receiving Oral Cancer Surgery: Interim Analysis from the COOLS Trial

505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was

Synthetic erythropoiesis stimulating proteins

33,344 (95% CI,

Pseudo native chemical ligation

31,553–

Total Chemical Synthesis of a 27 kDa TASP Protein Derived from the MscL Ion Channel of M. tuberculosis by Ketoxime-Forming Ligation

34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, (

Binding and Uptake of RGD-Containing Ligands to Cellular αvβ3 Integrins

47,792; 95% CI,