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• W2608271607 endingPage "3340" @default.
• W2608271607 startingPage "3329" @default.
• W2608271607 abstract "Recent studies have revealed that the epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) are overexpressed in various types of human tumors and are attractive targets for anticancer drugs. In the present study, the expression of EGFR and IGF-1R in esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues in a tissue microarray was firstly detected by immunohistochemical staining. In addition, their co-overexpression was observed in 48 out of 75 (64%) patients. Based on the findings, the antitumor activity of an EGFR/IGF-1R bispecific and enediyne-energized fusion protein EGF-LDP-IGF-AE, which we constructed recently by fusing two ligands (EGF and IGF-1) with an enediyne antibiotic lidamycin (LDM), on ESCC were evaluated. Binding assay indicated that the EGF-LDP-IGF protein bound to esophageal cancer cells, and then internalized into the cytoplasm. In vitro, the enediyne‑energized fusion protein EGF-LDP-IGF-AE exhibited extremely potent cytotoxicity to ESCC cells with IC50 values between 10-10 and 10-15 mol/l. In vivo, EGF-LDP‑IGF-AE also markedly suppressed the growth of human KYSE450 xenografts by 75.1% when administered at 0.3 mg/kg in a nude mouse model, and its efficacy was significantly higher than that of LDM (at maximum tolerated dosage) and mono-specific counterparts. In addition, EGF-LDP-IGF-AE arrested cell cycle progression and it concentration-dependently induced cell apoptosis as well as inhibited the activation of EGFR/IGF-1R and two major downstream signaling pathways (PI3K/AKT and RAS/MAPK). These data imply the potential clinical application of EGF-LDP-IGF-AE for ESCC patients with EGFR and/or IGF-1R overexpression." @default.
• W2608271607 created "2017-05-05" @default.
• W2608271607 creator A5005246589 @default.
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• W2608271607 date "2017-04-27" @default.
• W2608271607 modified "2023-10-18" @default.
• W2608271607 title "A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer" @default.
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• W2608271607 doi "https://doi.org/10.3892/or.2017.5606" @default.
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• W2608271607 hasPublicationYear "2017" @default.
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