• Title/Summary/Keyword: Human epidermal growth factor

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Epidermal Growth Factor Receptor-Related DNA Repair and Radiation-Resistance Regulatory Mechanisms: A Mini-Review

  • Bai, Jing;Guo, Xiao-Guang;Bai, Xiao-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4879-4881
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    • 2012
  • Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. The EGFR modulates DNA repair after radiation-induced damage through an association with the catalytic subunit of DNA protein kinase. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation, and non-homologous end joining is the predominant pathway for repair of radiation-induced DSBs. Some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer. These pathways also invoke the cell survival mechanisms that lead to resistance to radiation. The molecular connection between the EGFR and its control over DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this mini-review was not only to highlight the relation of the EGFR signal as a regulatory mechanism to DNA repair and radiation resistance, but also to provide clues to improving existing radiation resistance through novel therapies based on the above-mentioned mechanism.

The Effect of Epidermal Growth Factor on Cell Proliferation and Its Related Signal Pathways in Pig Hepatocytes

  • Kim Dong-Il;Han Ho-Jae;Park Soo-Hyun
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.249-254
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    • 2006
  • It has been reported that liver is a very important organ to xenotransplantation. Pig is known to be a most suitable species in transplantation of human organs. However, the physiological function of pig hepatocytes is not clear elucidated. Epidermal growth factor (EGF) is known to be a mitogen in various cell systems. Thus, we examined the effect of EGF on cell proliferation and its related signal cascades in primary cultured pig hepatocytes. EGF stimulates cell proliferation in a dose (>1ng/ml) dependent manner. EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by AG 1478 ($10^{-6}M$, an EGF receptor antagonist) genistein and herbymycin A (tyrosine kinase inhibitors, $10^{-6}M$), suggesting the role of activation and tyrosine phosphorylation of EGF receptor. In addition, EGF-induced increase of $[^3H]-thymidine$ incorporation was prevented by neomycin $(10^{-4}M)$, U73122 $(10^{-5}M)$ (phospholipase C [PLC] inhibitors), staurosporine ($(10^{-8}M)$, or bisindolylmaleimide I $(10^{-6}M)$ (protein kinase C [PKC] inhibitors), suggesting the role of PLC and PKC. Moreover, EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by PD 98059 (a p44/42 mitogen activated protein kinase [MAPK] inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor). EGF increased the translocation of PKC from cytosol to membrane fraction and activated p42/44 MAPK, p38 MAPK and JNK. In conclusion, EGF stimulates cell proliferation via PKC and MAPK in cultured pig hepatocytes.

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Topical Use of Recombinant Human Epidermal Growth Factor (EGF)-Based Cream to Prevent Radiation Dermatitis in Breast Cancer Patients: a Single-Blind Randomized Preliminary Study

  • Kong, Moonkyoo;Hong, Seong Eon
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4859-4864
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    • 2013
  • Background: The purpose of this study was to assess the effectiveness of a recombinant human epidermal growth factor (EGF)-based cream for the prevention of acute radiation dermatitis in breast cancer patients receiving radiotherapy (RT). Materials and Methods: Between December 2012 and April 2013, 40 breast cancer patients who received postoperative RT were prospectively enrolled in this study and randomly assigned to receive human recombinant EGF-based cream (intervention group) or general supportive skin care (control group). The grade of radiation dermatitis and pain score were examined at weekly intervals during RT and 6 weeks after RT completion. Results: All patients completed the planned RT and complied well with instructions for applying the study cream and general supportive skin care. In the intervention group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 3 (15%), 11 (55%), and 6 patients (30%), respectively. In comparison, in the control group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 8 (40%), 10 (50%), and 2 patients (10%), respectively. The intervention group showed lower incidence of grade 3 radiation dermatitis than the control group (p=0.068 in univariate analysis and p=0.035 in multivariate analysis). There was no statistically significant difference in the maximal pain score between the two groups (p=0.934). Conclusions: This single-blind randomized preliminary study showed that recombinant human EGF-based cream can have a beneficial role in preventing or minimizing radiation dermatitis in breast cancer patients. To confirm the results of our study, additional studies with a large sample size are required.

Preparation and stability of N-terminal PEGylated Recombinant Human Epidermal Growth Factor

  • Na, Dong-Hee;Youn, Yu-Seok;Park, Chong-Jeon;Lee, Sang-Deuk;Lee, Kang-Choon
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.415.3-416
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    • 2002
  • To improve the stability of recombinant human epidermal growth factor (rhEGF) as therapeutic agent. the N-terminal PEGylated rhEGF (N-PEG-rhEGF) was prepared by site-specific bioconjugation and the stability was investigated in rat skin wound homogenates. Two different N-PEG-rhGEFs (N-PEG5K- and N-PEG20K-rhEGF) were successfully prepared with the yields of above 70%. The PEGylation site was directly confirmed by determining the molecular mass of Lys-C digested samples using MALDI- TOF MS. (omitted)

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Expression of Recombinant Epidermal Growth Factor in E. coli

  • Chang Shin Yoon;Eun
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.2 no.2
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    • pp.86-89
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    • 1997
  • Epidermal growth factor(EGF) known as a urgastrone is a powerful mitogen with a wide variety of possibilities for medical usages. A mature EGF coding region was isolated from human prepro-EGF sequence by a conventional PCR and cloned into pQE vector in which the gene product was supposed to be expressed with 6$\times$His tag for the subsequent purification. The recombinant mature EGF was expressed in M15[Rep4], an Escherichia coli host strain, in amount of 30-40% of total proteins pressent in E. coli extract by the addition of isopropylthio-$\beta$-galactopyranoside (IPTG). The recombinant EGF purified using a Ni2+-NTA affinity colume chromatography was active in its ability to induce phosphorylation on tyrosine residues of several substrate proteins when murine NH3T3 and human MRC-5 fibroblast cells were stimulated with it. This work may provide the basic technology and information for the production of recombinant EGF.

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Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • v.34 no.1
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    • pp.1-9
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    • 2016
  • Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

General Pharmacology of DWP 401, a Recombinant Human Epidermal Growth Factor (재조합 인간 상피세포 성장인자(DWP 401)의 일반약리작용)

  • 천선아;김상미;이은방;임승욱;유영효;박명환
    • YAKHAK HOEJI
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    • v.39 no.5
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    • pp.471-479
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    • 1995
  • The recombinant human epidermal growth factor(DWP 401) was investigated on the pharrnacological actions. DWP 401 had no effects on the hexobarbital-induced sleeping time, locomotor activity, rotarod test, body temperature, analgesic action and anticonvulsant action in mice. It also had no influences on the isolated tracheal muscle and ileum of guinea-pig, isolated uterus and fundus strip of rats. Slight hypotensive action with effect on respiration was revealed at a dose of 8 g/kg i.v. of DWP 401 in rabbits. DWP 401 exhibited a weak inhibitory action of glucose tolerance in normal rats, significantly lowered the blood glucose contents in adrenalectomized rats at .a concentration of 160 g,/kg, and produced a significant inhibitory effect on leucocyte migration in CMC-pouch of rats at a concentration of 32 g/rat. Furthermore, DWP 401 showed a significant decrease on gastric juice volume and acidity. However. DWP 401 had no intestinal propulsion rate and influence on urine excretion.

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Thermosensitive Chitosan-based Hydrogel with Growth Factor as Adhesion Barrier (성장인자/키토산이 담지된 온도감응성 하이드로젤의 유착방지제로서의 응용)

  • Park, Jun-Kyu;Nah, Jae-Woon;Choi, Changyong
    • Polymer(Korea)
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    • v.39 no.3
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    • pp.480-486
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    • 2015
  • The adhesion of tissue and organ occur with frequency after surgery. Theomosensitive hydrogel was prepared from poloxamer/chitosan/epidermal growth factor as adhesion barrier agent. The prepared hydrogel showed sol-gel transition temperatures around human temperature and gelation temperature was the faster within 1 min. The hydrogel sustained the release of epidermal grow factor during 7 days. The hydrogel was highly effective for the prevention of tissue and organ adhesion in rat model. The thermosensitive and antibacterial chitosan hydrogel can be useful to consider the anti-adhesion barrier with increased adhesion of organ and sustained release of epidermal growth factor.

Analysis of the effect of trichloroacetic acid and epidermal growth factor release on cytoskeleton gene expression using the nano-controlled releasing system (나노방출제어시스템을 이용한 trichloroacetic acid와 epidermal growth factor 방출이 세포골격형성 유전자 발현에 미치는 영향 분석)

  • Park, Mi Jeong;Leesungbok, Richard;Lee, Suk Won
    • The Journal of Korean Academy of Prosthodontics
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    • v.58 no.4
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    • pp.290-299
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    • 2020
  • Purpose: Here, we verified that the actin cytoskeletal gene expression of human gingival fibroblasts was altered by the administration of trichloroacetic acid (TCA) and epidermal growth factor (EGF) using the nano-controlled releasing system. Materials and methods: The control and experimental groups were divided into 3 groups: the group with the TCA-only nano-controlled releasing system (EXP1), the group with the TCA- and EGF nano-controlled releasing system (EXP2), and the control group (CON) with 48-h incubation. Expression of 26 genes involved in the regulation of actin cytoskeleton were analyzed by real-time PCR followed by the determination of correlations and influential factors using the Pearson correlation analysis and multiple regression analysis. Results: Among 23 genes upregulated in EXP1 and EXP2, expression of 14 genes were significantly increased in EXP2 compared to EXP1. On the other hand, LPAR1 was downregulated only in EXP1, GNA13 was upregulated only in EXP2, and F2R was downregulated only in EXP2. Three Rac1-related genes and CDC42 were identified as the influential factors of the actin gene upregulation. Conclusion: The actin cytoskeleton genes in human gingival fibroblast were upregulated by the administration of TCA and EGF using HGC-based nano-controlled releasing system.