Epidermal Growth Factor Target Research Articles

Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy.

The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to 18F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (124I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 μCi/mouse.

Sex Difference in the Expression and Gene Network of Epidermal Growth Factor Receptor in Pituitary Gland in Mice

Background: Epidermal growth factor receptor (EGFR) involves in diverse cellular functions and plays an important role in the pathogenesis of many malignancies in the human population. The pituitary gland is a target of epidermal growth factor (EGF) and it is well known that EGFR plays a role in pituitary tumor as well as other tumors formation and progression. Methods: In this study, we have screened expression profiles for the whole genome of pituitary genes of both sexes from multiple mouse recombinant inbred strains. In addition, using Network Graph, we have constructed the gene network in combination with the correlation matrix. To determine the chromosomal locations that regulate the expression of Egfr in females and males, the transcriptome mapping was conducted using Gene Network mapping tool. Furthermore, we conducted bioinformatics analysis to identify genes that have been reported to regulate or functionally connect to Egfr. Results: Statistical analysis of Egfr expression levels between female and male mice produced a P value of 1.56442E-09. The R value obtained from the correlation analysis is 0.22. A considerable number of genes in the gene network of Egfr showed sex difference. These genes are known important in caner pathways. The eQTLs that regulate the expression levels of Egfr also showed sex difference. Gender difference of the correlations between Egfr expression levels and the T cell growth is also observed. Conclusion: Our data suggest that sex difference in the expression levels of Egfr may have a significant impact on immunological disorders.

3D-QSAR and molecular docking studies of 4-anilinoquinazoline derivatives: a rational approach to anticancer drug design

The present article is an attempt to formulate the three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling of 4-anilinoquinazoline derivatives having promising anticancer activities inhibiting epidermal growth factor (EGFR) kinase. Molecular field analysis was applied for the generation of steric and electrostatic descriptors based on aligned structures. Partial least-squares (PLS) method was applied for QSAR model development considering training and test set approaches. The PLS models showed some interesting results in terms of internal and external predictability against EGFR kinase inhibition for such type of anilinoquinazoline derivatives. Steric and electrostatic field effects are discussed in the light of contribution plot generated. Finally, molecular docking analysis was carried out to better understand of the interactions between EGFR target and inhibitors in this series. Hydrophobic and hydrogen-bond interactions lead to identification of active binding sites of EGFR protein in the docked complex.

An NRSF/REST-like repressor downstream of Ebi/SMRTER/Su(H) regulates eye development in Drosophila.

The corepressor complex that includes Ebi and SMRTER is a target of epidermal growth factor (EGF) and Notch signaling pathways and regulates Delta (Dl)-mediated induction of support cells adjacent to photoreceptor neurons of the Drosophila eye. We describe a mechanism by which the Ebi/SMRTER corepressor complex maintains Dl expression. We identified a gene, charlatan (chn), which encodes a C2H2-type zinc-finger protein resembling human neuronal restricted silencing factor/repressor element RE-1 silencing transcription factor (NRSF/REST). The Ebi/SMRTER corepressor complex represses chn transcription by competing with the activation complex that includes the Notch intracellular domain (NICD). Chn represses Dl expression and is critical for the initiation of eye development. Thus, under EGF signaling, double negative regulation mediated by the Ebi/SMRTER corepressor complex and an NRSF/REST-like factor, Chn, maintains inductive activity in developing photoreceptor cells by promoting Dl expression.