Cellular Hyperplasia in Rats Following Continuous Intravenous Infusion of Recombinant Human Epidermal Growth Factor

In this study, we determined in vivo morphologic effects of continuous intravenous infusion of recombinant human epidermal growth factor (EGF) in adult Wistar rats. The EGF used consisted of the amino acid residues 1-48 of the human 53-amino-acid EGF molecule, purified from transfected Escherichia coli. Doses of 25, 100, or 250 μg/kg body weight were administered using Harvard digital syringe infusion pumps for 4 weeks. At necropsy, the submandibular salivary glands, Harderian glands, liver, kidneys (females only), and ovaries were enlarged and urinary bladders were thickened in 100- and 250-μg/kg rats. Numerous tissues of the 100- and 250-μg/kg rats contained hyperplastic epithelial cells, and selected organs also had mesenchymal cell proliferation. Epithelial proliferation was most pronounced in the trachea, nasal cavity, nasolacrimal duct, tongue, stomach, small intestine, large intestine, urinary tract, salivary gland ducts, and Harderian gland. Periportal hepatocytes were hypertrophic, correlating with increased liver weight. In addition, mesenchymal cell proliferation was evident in the gastric mucosa lamina propria and in heart valves in 100- and 250-μg/kg rats. Increased ovarian weight correlated with increased number and size of corpora lutea and an increased incidence of luteal cysts. Continuous systemic exposure of adult Wistar rats to high doses of EGF resulted in generalized epithelial hyperplasia and tissue-selective mesenchymal proliferation.

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Abstract B099: Characterization of monoclonal antibodies generated to the 287-302 amino acid loop of the human epidermal growth factor receptor

10.1158/1535-7163.targ-19-b099 ◽

2019 ◽

Author(s):

Eric Chun Hei Ho ◽

Antonella Antignani ◽

Robert Sarnovsky ◽

David J FitzGerald

Keyword(s):

Epidermal Growth Factor Receptor ◽

Monoclonal Antibodies ◽

Amino Acid ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Human Epidermal Growth Factor ◽

Epidermal Growth

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Size effect of human epidermal growth factor-conjugated polystyrene particles on cell proliferation

Biomaterials Science ◽

10.1039/d0bm00183j ◽

2020 ◽

Vol 8 (17) ◽

pp. 4832-4840

Author(s):

Setayesh Yasami-Khiabani ◽

Akbar Karkhaneh ◽

Mohammad Ali Shokrgozar ◽

Amir Amanzadeh ◽

Majid Golkar

Keyword(s):

Cell Proliferation ◽

Growth Factors ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Size Effect ◽

Human Epidermal Growth Factor ◽

Therapeutic Molecules ◽

Epidermal Growth

Conjugation of growth factors to a carrier is a favorable method to improve their efficacy as therapeutic molecules.

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Epidermal growth factor: Modulator of murine embryonic palate mesenchymal cell proliferation, polyamine biosynthesis, and polyamine transport

Journal of Cellular Physiology ◽

10.1002/jcp.1041400222 ◽

1989 ◽

Vol 140 (2) ◽

pp. 359-370 ◽

Cited By ~ 28

Author(s):

Kathleen J. Gawel-Thompson ◽

Robert M. Greene

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Mesenchymal Cell ◽

Polyamine Biosynthesis ◽

Polyamine Transport ◽

Epidermal Growth

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Human epidermal growth factor-functionalized cocoon silk with improved cell proliferation activity for the fabrication of wound dressings

Journal of Biomaterials Applications ◽

10.1177/0885328221997981 ◽

2021 ◽

pp. 088532822199798

Author(s):

Meiyu Wu ◽

Shenyu Huang ◽

Xiaogang Ye ◽

Jinghua Ruan ◽

Shuo Zhao ◽

...

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Fiber Surface ◽

Cost Effective ◽

Wound Dressings ◽

Wild Type ◽

Transgenic Silkworm ◽

Human Epidermal Growth Factor ◽

Epidermal Growth

Human epidermal growth factor (hEGF) is a key factor involved in wound healing owing to its powerful ability to stimulate cell proliferation. In this study, we used piggyBac transposon technology to produce transgenic silkworms expressing the hEGF protein fused to truncated heavy chain (FibH-hEGF). The FibH–hEGF fusion protein was successfully expressed and secreted into silkworm cocoons. Compared to wild-type silk, the transgenic silkworm silk had the similar morphology about silks fiber surface and cocoon nets, while the secondary structure between the transgenic silk and wild-type silk was different. Most importantly, transgenic silkworm cocoon silk powder extract significantly increased human fibroblast FIB cell proliferation for a long duration with no apparent cytotoxicity. Our study provides a promising method for obtaining cost-effective and functional biomaterials for the fabrication of wound dressings.

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A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

10.21203/rs.3.rs-1124196/v1 ◽

2022 ◽

Author(s):

Fangfang Ding ◽

Jie Huang ◽

Zeying Feng ◽

Yun Kuang ◽

Shuang Yang ◽

...

Keyword(s):

Monoclonal Antibody ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Intravenous Infusion ◽

Growth Factor Receptor ◽

Human Epidermal Growth Factor ◽

Recombinant Monoclonal Antibody ◽

Epidermal Growth ◽

Antibody Targeting

Abstract Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021

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Biosynthesis of a protein containing a nonprotein amino acid by Escherichia coli: L-2-aminohexanoic acid at position 21 in human epidermal growth factor.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.85.17.6237 ◽

1988 ◽

Vol 85 (17) ◽

pp. 6237-6241 ◽

Cited By ~ 34

Author(s):

H. Koide ◽

S. Yokoyama ◽

G. Kawai ◽

J. M. Ha ◽

T. Oka ◽

...

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Human Epidermal Growth Factor ◽

Nonprotein Amino Acid ◽

Epidermal Growth

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Quantitatively Mapping the Interaction of HER2 and EGFR on Cell Membranes with Peptide Probes

Nanoscale ◽

10.1039/d1nr02684d ◽

2021 ◽

Author(s):

Qiuyan Yan ◽

Mingjun Cai ◽

Yingying Jing ◽

Hongru Li ◽

Haijiao Xu ◽

...

Keyword(s):

Cell Proliferation ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Biological Processes ◽

Her Family ◽

Human Epidermal Growth Factor ◽

Epidermal Growth ◽

Peptide Probes

Human epidermal growth factor receptor-2 (HER2) is a member of the epidermal growth factor receptor (HER) family that involved in various biological processes such as cell proliferation, survival, differentiation, migration...

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Aromaticity at position 37 in human epidermal growth factor is not obligatory for activity.

Molecular and Cellular Biology ◽

10.1128/mcb.11.5.2425 ◽

1991 ◽

Vol 11 (5) ◽

pp. 2425-2431 ◽

Cited By ~ 15

Author(s):

D A Engler ◽

M R Hauser ◽

J S Cook ◽

S K Niyogi

Keyword(s):

Amino Acids ◽

Biological Activity ◽

Amino Acid ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Aromatic Amino Acid ◽

Transforming Growth Factor ◽

Site Directed Mutagenesis ◽

Human Epidermal Growth Factor ◽

Epidermal Growth

The third disulfide loop (amino acids 33 to 42) of human epidermal growth factor (hEGF) encompasses the region of highest amino acid conservation among all of the EGF-like family of molecules. The importance of some of these highly conserved residues for the maintenance of biological activity, especially the aromatic amino acid tyrosine at position 37, has until now been considered essential on the basis of previous studies with the EGF-like molecule transforming growth factor alpha. Variants at the Tyr-37 position of hEGF were constructed by site-directed mutagenesis. The substituting amino acids were phenylalanine, histidine, serine, alanine, aspartic acid, arginine, and glycine. The variants were tested for their ability to competitively displace native [125I]hEGF from its receptor and to stimulate the protein-tyrosine kinase activity of the receptor; the order of efficacy of substituting amino acids was Phe greater than His greater than Ser greater than Ala greater than Asp greater than Arg greater than Gly in both assays. All were effective, with no or only moderate reduction in potency, in stimulating the incorporation of [3H]thymidine into acid-insoluble material of quiescent mouse A31 cells. Only Tyr-37----Ala, Tyr-37----Arg and Tyr-37----Gly were slightly less potent in the cell assay. Thus, neither tyrosine nor another aromatic amino acid at position 37 in hEGF is essential for full biological activity.

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