Kinetic Analysis of In Vivo Receptor-Dependent Binding of Human Epidermal Growth Factor by Rat Tissues

1988 ◽  
Vol 77 (3) ◽  
pp. 200-207 ◽  
Author(s):  
Dong Chool Kim ◽  
Yuichi Sugiyama ◽  
Hiroaki Satoh ◽  
Tohru Fuwa ◽  
Tatsuji Iga ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinetic Analysis ◽  
Rat Tissues ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Kinetic analysis of the downregulation of epidermal growth factor receptors in rats in vivo

1990 ◽  
Vol 258 (4) ◽  
pp. C593-C598 ◽  
Author(s):  
S. Yanai ◽  
Y. Sugiyama ◽  
T. Iga ◽  
T. Fuwa ◽  
M. Hanano
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Kinetic Analysis ◽  
Intravenous Administration ◽  
Recovery Rate ◽  
Specific Binding ◽  
Control Level ◽  
Epidermal Growth

We previously clarified the specific binding sites for epidermal growth factor (EGF) in several organs in rats based on in vivo kinetic analysis (D. C. Kim, Y. Sugiyama, H. Sato, T. Fuwa, T. Iga, and M. Hanano. J. Pharm. Sci. 77: 200-207, 1988). In the present study, we have determined the extent of the receptor downregulation and the recovery rate of the available receptors for EGF in several organs in vivo. At the specified times (30 min-24 h) after intravenous administration of excess unlabeled EGF (300 micrograms/kg), the early-phase (less than 3 min) uptake clearances (k1) of the tracer amount of 125I-EGF, which are proportional to the cell-surface available receptor densities, were determined in the liver, kidney, duodenum, jejunum, ileum, stomach, and spleen. As the result, the k1 value in each organ at 30 min after intravenous administration of unlabeled EGF was lowered close to the receptor-independent clearance value, indicating that the cell-surface receptors were almost completely downregulated, and thereafter, the k1 value showed gradual recovery to the control level. Furthermore, the recovery half-lives showed interorgan differences, namely the half-life (20 min) in the liver was much shorter than those (2-4.5 h) in other organs. These results were considered to reflect the processes of the recycling of internalized EGF receptors to the cell-surface or recruitment of new receptors. It was concluded that the recovery rate of the downregulated receptors in the liver, which is most responsible for the plasma clearance of EGF, is much faster than those in other organs.

scholarly journals Microencapsulated Recombinant Human Epidermal Growth Factor Ameliorates Osteoarthritis in a Murine Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shih-Chao Lin ◽  
Xiang Zhang ◽  
Shiow-Yi Chen ◽  
Chi-Chien Lin ◽  
Yen-Shuo Chiu
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Platelet Rich Plasma ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Human Epidermal Growth Factor ◽  
Age Related ◽  
Epidermal Growth

Osteoarthritis, a highly age-related and chronic inflammatory disorder with cartilage loss, causes patients difficultly in movement; there is no efficient and sustainable remedy for osteoarthritis currently. Although hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). In the current study, we induced the osteoarthritis-like symptoms with monosodium iodoacetate (MIA) in rats and investigated the therapeutic effects of Me-rhEGF. Following administration of HA/Me-rhEGF in vivo, we observed that the total Mankin scores, cartilage oligomeric protein, C-telopeptide of type II collagen, IL-1β, IL-6, IL-17A, and TNF-α cytokines, nitric oxide, and prostaglandin E2 expressions were significantly inhibited. Our results also strongly indicate that individual use of HA or rhEGF slightly decreased the inflammation and restored the destructive joint structure, but was not as drastic as seen in the HA/Me-rhEGF. Moreover, HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. These findings reveal that the treatment of HA/Me-rhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. In essence, we believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis.

In Vivo Chemoenzymatic Control of N-Terminal Processing in Recombinant Human Epidermal Growth Factor

ChemBioChem ◽  
2007 ◽  
Vol 8 (18) ◽  
pp. 2227-2232 ◽  
Author(s):  
Lars Merkel ◽  
Yuri Cheburkin ◽  
Birgit Wiltschi ◽  
Nediljko Budisa
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

scholarly journals FTY720 in resistant human epidermal growth factor receptor 2-positive breast cancer

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei-Pang Chung ◽  
Wei-Lun Huang ◽  
Wei-An Liao ◽  
Chun-Hua Hung ◽  
Chi-Wu Chiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Positive Breast Cancer

AbstractThe prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer has considerably improved. However, no reliable treatment besides anti-HER2 strategies has been available. FTY720, a small-molecule compound used for treating refractory multiple sclerosis, has been reported to have beneficial effects against cancers. We therefore evaluated the efficacy of FTY720 in trastuzumab-resistant breast cancer cells and investigated the possible mechanism involved. This study evaluated morphological changes after FTY720 treatment. Antiproliferative WST-1 assays and LDH Cytotoxicity Assay Kits were used to determine the treatment effects of drugs, whereas Western blot analysis was used to evaluate protein expression. Apoptotic events were investigated through annexin V staining and TUNEL assays using flow cytometry. FTY720 was effective in trastuzumab-resistant breast cancer cell lines despite the presence of PIK3CA mutation. Studied on a xenograft mouse model, FTY720-treated groups had statistically significantly poorer HCC1954 xenograft growth in vivo compared with the control group. Our findings suggest that FTY720 can overcome resistance to trastuzumab therapy in patients with HER2-positive breast cancer, with FTY720 plus trastuzumab might offer even better efficacy in vitro and in vivo.

scholarly journals Recombinant Human Epidermal Growth Factor Accelerates the Proliferation of Irradiated Human Fibroblasts and Keratinocytes in vitro and in vivo

2009 ◽  
Vol 50 (6) ◽  
pp. 545-552 ◽  
Author(s):  
Seung-Hee RYU ◽  
Soo Young MOON ◽  
Youn-Joo YANG ◽  
Sun Rock MOON ◽  
Joon Pio HONG ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Fibroblasts ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth
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