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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antibodies, Monoclonal, Antineoplastic Agents, Blotting, Western, Cell Line, Tumor, Cross-Linking Reagents, Dimerization, Epidermal Growth Factor, ErbB Receptors, Gefitinib, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Iodine Radioisotopes, Isotope Labeling, Panitumumab, Phosphorylation, Protein-Tyrosine Kinases, Quinazolines.
user
Is significant increase in hEGF uptake correlated with formation of EGFR dimers induced by the EGFR tyrosine kinase inhibitor gefitinib? Context: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) is approved for cancer treatment. We investigated whether gefitinib treatment can enhance human EGF (hEGF) uptake in vitro, thereby increasing the potential of hEGF as a vehicle for EGFR-targeted therapy. Western blotting was used to detect the effect of gefitinib on EGFR signaling. Different EGFR-expressing tumor cells (SCC-1, 22B, A549, and HT-29) were pretreated with gefitinib, and then with (125)I-hEGF or (125)I-Vectibix (an anti-EGFR monoclonal antibody). Cell-associated activity was then measured. A cross-linking assay detected increased EGFR dimer formation in gefitinib-treated cells. Total EGFR levels were not changed, but EGFR phosphorylation was reduced in cells pretreated with gefitinib. Gefitinib mediated formation of EGFR dimers; binding of (125)I-hEGF to cells pretreated with gefitinib significantly increased. In contrast, binding of (125)I-Vectibix to tumor cells did not increase. Although total EGFR levels did not increase, binding of hEGF to EGFR + tumors was significantly enhanced after gefitinib treatment, because of increased hEGF binding to gefitinib-induced EGFR dimers.
assistant
These results suggest that hEGF could enhance EGFR-targeting when used with gefitinib. Final Decision: yes