Receptor tyrosine kinases (RTKs) regulate many cellular functions and are important targets in pharmaceutical development, particularly in cancer treatment. EGFR and EphA2 are two key RTKs that are associated with oncogenic phenotypes. Several studies have reported functional interplay between these receptors, but the mechanism of interaction is still unresolved.
View Article and Find Full Text PDFThe epidermal growth factor (EGF) receptor (EGFR) is activated by the binding of one of seven EGF-like ligands to its ectodomain. Ligand binding results in EGFR dimerization and stabilization of the active receptor conformation subsequently leading to activation of downstream signaling. Aberrant activation of EGFR contributes to cancer progression through EGFR overexpression/amplification, modulation of its positive and negative regulators, and/or activating mutations within EGFR.
View Article and Find Full Text PDFJAMIA Open
October 2024
Curr Opin Chem Biol
August 2024
As a time-domain analogue of fluorescence imaging, FCS offers valuable insights into molecular dynamics, interactions, and concentrations within living cells. The primary insight generated by FCS is molecular mobility and concentration, which makes it useful for investigating molecular-scale details without the need for enrichment or separation. A specific strength of FCS is the ability to probe protein-protein interactions in live cells and several recent applications in this area are summarized.
View Article and Find Full Text PDFReceptor tyrosine kinases (RTKs) regulate many cellular functions and are important targets in pharmaceutical development, particularly in cancer treatment. EGFR and EphA2 are two key RTKs that are associated with oncogenic phenotypes. Several studies have reported functional interplay between these receptors, but the mechanism of interaction is still unresolved.
View Article and Find Full Text PDFVasorin (VASN), a transmembrane protein heavily expressed in endothelial cells, has garnered recent interest due to its key role in vascular development and pathology. The oligomeric state of VASN is a crucial piece of knowledge given that receptor clustering is a frequent regulatory mechanism in downstream signaling activation and amplification. However, documentation of VASN oligomerization is currently absent.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2024
While the existence and functional role of class C G-protein-coupled receptors (GPCR) dimers is well established, there is still a lack of consensus regarding class A and B GPCR multimerization. This lack of consensus is largely due to the inherent challenges of demonstrating the presence of multimeric receptor complexes in a physiologically relevant cellular context. The C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR that is a promising target of anticancer therapy.
View Article and Find Full Text PDFBackground: A cancer diagnosis may have deleterious effects on health-related quality of life (HRQOL) as adults age. This study examined differences in HRQOL between cancer and matched noncancer Medicare beneficiaries over 65, within and across two time periods.
Methods: We used novel matching methods on data from the Surveillance, Epidemiology and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data resource.
Background: This study aimed to identify the most common types of nontraumatic dental conditions (NTDCs) before and during the COVID-19 pandemic and assess the variations in the most common NTDCs by patient age groups and rural or urban locations and the impact of COVID-19 on emergency department (ED) visits for NTDCs in North Carolina.
Methods: The authors conducted a retrospective data analysis of ED data from the North Carolina Disease Event Tracking and Epidemiology Collection Tool. The authors estimated the proportions of NTDCs of all ED visits in 2019 and 2021 and ranked the proportions of the major categories of NTDCs by age groups and rural or urban locations.
Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that initiates both ligand-dependent tumor-suppressive and ligand-independent oncogenic signaling. We used time-resolved, live-cell fluorescence spectroscopy to show that the ligand-free EphA2 assembles into multimers driven by two types of intermolecular interactions in the ectodomain. The first type entails extended symmetric interactions required for ligand-induced receptor clustering and tumor-suppressive signaling that inhibits activity of the oncogenic extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) protein kinases and suppresses cell migration.
View Article and Find Full Text PDFJ Natl Cancer Inst
October 2023
To develop and validate a predictive algorithm that identifies pediatric patients at risk of asthma-related emergencies, and to test whether algorithm performance can be improved in an external site via local retraining. In a retrospective cohort at the first site, data from 26 008 patients with asthma aged 2-18 years (2012-2017) were used to develop a lasso-regularized logistic regression model predicting emergency department visits for asthma within one year of a primary care encounter, known as the Asthma Emergency Risk (AER) score. Internal validation was conducted on 8634 patient encounters from 2018.
View Article and Find Full Text PDFThe epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) commonly targeted for inhibition by anticancer therapeutics. Current therapeutics target EGFR's kinase domain or extracellular region. However, these types of inhibitors are not specific for tumors over healthy tissue and therefore cause undesirable side effects.
View Article and Find Full Text PDFIn multiple sclerosis (MS), demyelination occurs in the cerebral cortex, and cerebral cortex atrophy correlates with clinical disabilities. Treatments are needed in MS to induce remyelination. Pregnancy is protective in MS.
View Article and Find Full Text PDFA large repertoire of nanocarrier (NC) technologies exists, each with highly specified advantages in terms of targetability, stability, and immunological inertness. The characterization of such NC properties within physiological conditions is essential for the development of optimized drug delivery systems. One method that is well established for reducing premature elimination by avoiding protein adsorption on NCs is surface functionalization with poly(ethylene glycol) (PEG), aptly called PEGylation.
View Article and Find Full Text PDFBackground: People with cancer experience symptoms that adversely affect quality of life. Despite existing interventions and clinical guidelines, timely symptom management remains uneven in oncology care. We describe a study to implement and evaluate an electronic health record (EHR)-integrated symptom monitoring and management program in adult outpatient cancer care.
View Article and Find Full Text PDFBackground: Cancer is a disease of aging, and most people with cancer are older than 65. However, widespread uptake of evidence-based approaches that facilitate quality care delivery for older adults with cancer are lacking. This project aimed to review National Institutes of Health (NIH) grants funded in the last decade that focused on healthcare delivery in aging and older adults with cancer, and to examine grant-related characteristics, study designs, and scientific topics included.
View Article and Find Full Text PDFPurpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years.
Methods And Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019.
Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15 to 30% of all non-small-cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function.
View Article and Find Full Text PDFEfforts to understand and mediate threats to water supplies rely on collection of reliable data at large scale, a goal which is often limited by availability of tools that are both affordable and reliable. We present here a low-cost, easy-to-use, do-it-yourself (DIY) spectrometer for measurement of a variety of relevant solute concentrations when coupled with inexpensive commercially-available reagents. Comparison of its performance with commercial options demonstrates the potential value of this device as transparent, versatile, and accurate-enough alternative for widespread application.
View Article and Find Full Text PDFTo examine mental health status, COVID-19 vaccine intention and barriers among college students in the U.S. Students ( = 337) registered at a large public university in 2021.
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