While epidermal growth factor (EGF) shows promise in addressing the clinical manifestations of intestinal ulcerative diseases by activating the EGF receptor (EGFR)-mediated cell signaling, its clinical application is hampered by poor protein hydrolytic stability, low thermostability, and difficulty in modification. The development of a novel EGFR agonist for ulcerative colitis remains an urgent need, necessitating innovative solutions to overcome the limitations of current therapies via recombinant EGF protein. Herein, we introduce a novel DNA agonist for EGFR, Dimer-YL, which employs a bivalent aptamer to induce stable receptor dimerization, thereby activating the EGFR signaling and related cell behaviors. Dimer-YL has been demonstrated to recapitulate the EGF-promoted cellular behaviors, including proliferation and migration, as well as repair the damage of intercellular tight junctions. Furthermore, our findings demonstrate the potent therapeutic function of Dimer-YL in alleviating DSS-induced ulcerative colitis in vivo. Together, the present work has revealed Dimer-YL as an innovative DNA molecule for effective EGFR activation, offering promise for the development of EGFR-agonistic agents for therapeutic purposes.

2023-07-15·Cancer Research and Treatment

Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers

Article

作者: Kim, Yongsub ; Lee, Joo Ho ; Kim, Jae Sik ; Jeon, Sang-Rok ; Jeon, Seung Hyuck ; Wu, Hong-Gyun

Purpose Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.Materials and Methods Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.Results We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

2023-04-01·Journal of Wound Care

Intralesional epidermal growth factor therapy in recalcitrant diabetic foot ulcers

Article

作者: Özker, Emre

Objectives:Diabetic foot ulcers (DFUs) cause high morbidity and mortality despite best treatment. Thus, new products are urgently needed to treat DFUs. Intralesional epidermal growth factor (EGF) (Heberprot-p) is considered to be an adjuvant therapy to standard of care (SOC) in DFUs. In the present study, the effect of Heberprot-p treatment on wound healing is compared to standard treatment.Methods:The data of patients with DFUs were retrospectively analysed. The patients who had had DFUs of at least four weeks' duration and who had been treated in the wound clinic between January 2014 and 2017 were included in the study. The patients were divided into study and control groups. The study group consisted of patients in whom intralesional recombinant human EGF, Heberprot-p 75μg, was applied; the control group consisted of the remaining patients in whom EGF was not applied. The efficacy of Heberprot-p treatment in Wagner 2 and 3 DFUs were retrospectively investigated.Results:The study group (n=29 patients) who received Heberprot-p treatment was found to have shorter treatment times and higher rates of wound healing than the control group (n=22 patients). Although the amputation rate in the study group was less than the control group, the difference was not statistically significant.Conclusion:Heberprot-p therapy is a promising treatment in DFUs, which can be routinely used as an adjunct to standard care.

100 项与癌症治疗用重组人表皮生长因子（EGF）偶联疫苗(Biotech Pharmaceuticals Pty Ltd) 相关的药物交易

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晚期非小细胞肺癌	临床1期	中国	北京精益泰翔技术发展有限公司	2012-04-10
晚期非小细胞肺癌	临床1期	中国	百泰生物药业有限公司	2012-04-10