Phage display peptides for breast cancer targeting

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Title from PDF of title page (University of Missouri--Columbia, viewed on April 15, 2011).Vita.Thesis advisor: Susan L. Deutscher"December 2010"M.S. University of Missouri-Columbia 2010.Cancer cell surfaces differ from healthy cell surfaces allowing the detection of cancer targets on the cell. Use of these targets combined with radiolabeled targeting vehicles results in sensitive imaging agents, with peptides identified as targeting vehicles. Human epidermal growth factor receptor 2 (ErbB-2) and galectin-3 (gal-3) are two targets for peptides, which have been shown to be over-expressed in a variety of tumors, including breast adenocarcinomas. ErbB-2 is involved in signal transduction pathways for cell growth and differentiation. Gal-3 is a lectin involved in carbohydrate-mediated cancer cell adhesion via contact with the tumor-specific Thomsen-Friedenreich (TF) disaccharide antigen, which increases metastasis from primary tumors. Bacteriophage (phage) display is a technique to select peptide sequences that bind to specific targets, such as ErbB-2 and gal-3. The target ErbB-2 was used to identify peptide KCCYSL. In this study, KCCYSL was radiolabeled by two different chelation chemistry methods and 99mTc to create two potential imaging agents. These radiolabeled peptides were analyzed both in vitro with breast cancer cell lines, and also in vivo performing biodistribution and breast tumor imaging studies in mouse models of breast cancer. Another target, gal-3, was used to identify peptide ANTPCGPYTHDCPVKR also using the phage display technique. In this study, to characterize the peptide and identify key residues for peptide interaction, in vitro cell binding and enzyme-linked immunosorbent assay experiments were done with alanine point mutation peptides.Includes bibliographical references

Evaluation of [99mTC(CO)3]-labeled ERBB-2-targeting peptides for breast carcinoma imaging [abstract]

The purpose of this study was to radiolabel a novel ErbB-2-avid peptide, discovered from bacteriophage display, with [99mTc(H2 O)3 (CO)3 ]+ and evaluate the in vitro cellular targeting and in vivo tumor imaging properties of the peptide in a mouse model of human breast cancer

Positional Cues in the Drosophila Nerve Cord: Semaphorins Pattern the Dorso-Ventral Axis

Positional cues target sensory axons to appropriate volumes of the developing nervous system independently of their synaptic partners

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Organization and Representation of Patient Safety Data: Current Status and Issues around Generalizability and Scalability

Recent reports have identified medical errors as a significant cause of morbidity and mortality among patients. A variety of approaches have been implemented to identify errors and their causes. These approaches include retrospective reporting and investigation of errors and adverse events and prospective analyses for identifying hazardous situations. The above approaches, along with other sources, contribute to data that are used to analyze patient safety risks. A variety of data structures and terminologies have been created to represent the information contained in these sources of patient safety data. Whereas many representations may be well suited to the particular safety application for which they were developed, such application-specific and often organization-specific representations limit the sharability of patient safety data. The result is that aggregation and comparison of safety data across organizations, practice domains, and applications is difficult at best. A common reference data model and a broadly applicable terminology for patient safety data are needed to aggregate safety data at the regional and national level and conduct large-scale studies of patient safety risks and interventions