Erythropoietin-producing hepatocellular (Eph) receptors are receptor tyrosine kinases involved in cell-cell contact. The EphA2 receptor is associated with cancer proliferation and migration. Therefore, EphA2 receptor imaging has the potential for cancer diagnosis. Here, we synthesized -(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[I]iodonicotinamide ([I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomography (SPECT) imaging of the EphA2 receptor. [I]ETB was designed on the basis of ALW-II-41-27, an inhibitor of EphA2 receptor kinase. Nonradioactive ETB was also synthesized and has been shown to efficiently inhibit EphA2 receptor kinase activity (IC: ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated that [I]ETB binds specifically to the EphA2 receptor. The biodistribution study of [I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00030 | DOI Listing |
Biomolecules
November 2024
Institute of Life Innovation Studies, Toyo University, Tokyo 115-8650, Japan.
Background: EphA2, a receptor-type tyrosine kinase, is overexpressed in several cancers, including colorectal cancer (CRC), and can be detected as soluble EphA2 in serum. This study aimed to investigate the relationship between soluble EphA2 and CRC.
Methods: Serum samples were collected from 65 patients with CRC and 19 healthy individuals.
Turk J Gastroenterol
December 2024
Department of Emergency Medicine, Shandong University, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Qingdao, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered the most widespread chronic liver condition globally. Genome-wide association studies (GWAS) have pinpointed several genetic loci correlated to MASLD, yet the biological significance of these loci remains poorly understood. Initially, we applied Functional Mapping and Annotation (FUMA) to conduct a functional annotation of the MASLD GWAS summary statistics, which included data from 3242 cases and 707 631 controls.
View Article and Find Full Text PDFClin Transl Med
January 2025
Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Queensland, Australia.
Background: Paediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma and osteosarcoma, represent a group of malignancies that significantly contribute to cancer-related morbidity and mortality in children and young adults. These cancers share common challenges, including high rates of metastasis, recurrence or treatment resistance, leading to a 5-year survival rate of approximately 20% for patients with advanced disease stages. Despite the critical need, therapeutic advancements have been limited over the past three decades.
View Article and Find Full Text PDFHeliyon
December 2024
Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Low-grade inflammation and pathological endochondral ossification are key processes underlying the progression of osteoarthritis, the most prevalent joint disease worldwide. In this study, we employed a multi-faceted approach, integrating publicly available datasets, analyses, experiments and models to identify new therapeutic candidates targeting these processes. Data mining of transcriptomic datasets identified EPHA2, a receptor tyrosine kinase associated with cancer, as being linked to both inflammation and endochondral ossification in osteoarthritis.
View Article and Find Full Text PDFJ Mol Cell Biol
December 2024
School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, United Kingdom.
Upon injury, fibroblasts in the surrounding tissue become activated, migrating into the wound in a controlled manner. Once they arrive, they contract the wound and remodel the stroma. While certain cell surface receptors promote fibroblast migration, others cause repulsion between fibroblasts upon contact, seemingly opposing their clustering within the wound bed.
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