• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.134-141
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• 2016

To investigate the role of polysaccharide from Acanthopanax senticosus (ASPS) in preventing lipopolysaccharide (LPS)-induced intestinal injury, 18 mice (at 5 wk of age) were assigned to three groups with 6 replicates of one mouse each. Mice were administrated by oral gavage with or without ASPS (300 mg/kg body weight) for 14 days and were injected with saline or LPS at 15 days. Intestinal samples were collected at 4 h post-challenge. The results showed that ASPS ameliorated LPS-induced deterioration of digestive ability of LPS-challenged mice, indicated by an increase in intestinal lactase activity (45%, p<0.05), and the intestinal morphology, as proved by improved villus height (20.84%, p<0.05) and villus height:crypt depth ratio (42%, p<0.05), and lower crypt depth in jejunum (15.55%, p<0.05), as well as enhanced intestinal tight junction proteins expression involving occludin-1 (71.43%, p<0.05). ASPS also prevented intestinal inflammation response, supported by decrease in intestinal inflammatory mediators including tumor necrosis factor ${\alpha}$ (22.28%, p<0.05) and heat shock protein (HSP70) (77.42%, p<0.05). In addition, intestinal mucus layers were also improved by ASPS, as indicated by the increase in number of goblet cells (24.89%, p<0.05) and intestinal trefoil peptide (17.75%, p<0.05). Finally, ASPS facilitated mRNA expression of epidermal growth factor (100%, p<0.05) and its receptor (200%, p<0.05) gene. These results indicate that ASPS can prevent intestinal mucosal barrier injury under inflammatory conditions, which may be associated with up-regulating gene mRNA expression of epidermal growth factor and its receptor.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.217-222
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• 2007

In the last 5 years the Epidermal Growth Factor Receptor (EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefits in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Also the targeting of the epithelial growth factor receptor (EGFR) kinase domain using the closely related inhibitors gefitinib and erlotinib has generally been ineffective against solid tumors, many of which over express the receptor. We found that there were some differential expressions according to primary antibodies of the EGFR protein which being used as one of the histological tumor markers for non-small cell lung cancer (NSCLC). We also found that there are some differential expressions according to antibodies, the pH of the antigen retrieval (AR) buffer solutions and kinds of enzymes. There were some differential expressions according to the secondary antibodies and the detection systems. We analyzed the correlations between the immunohistochemical expressions of the EGFR protein and the gene mutations of the EGFR. The differences between automatic stainers and manual staining methods were also evaluated.

• Molecules and Cells
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• v.20 no.2
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• pp.263-270
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• 2005

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 ($20{\mu}M$), a specific inhibitor of MMPs or AG1478 ($10{\mu}M$), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

• 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.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.107-108
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• 2003

The epidermal growth factor (EGF) is an important signaling ligand for the mitogenesis of many cells. The EGF receptors use signaling molecule multicomplexes and dynamic protein networks for the transmission and amplification of the signals as well as for the regulation of the cellular responses. EGF signaling has been reported to be enhanced in various tumors by the overexpressed EGF receptor and/or the mediators such as phospholipase C-$\gamma$1(PLC$\gamma$1). (omitted)

• Korean Journal of Cleft Lip And Palate
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• v.4 no.1
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• pp.13-26
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• 2001

Cleft lip and/or palate is the congenital orofacial malformation most commonly occurred in humans, The disease is multifactorial and is probably caused by genetic and/or environmental factors, So, there are many problems in research concerning etiology and in treatment of the disease, Even the most practiced and sophisticated methods of surgical repair are necessarily followed by scar contraction and fibrosis, which result in skeletal defects, dental abnormalities, cosmetic disfigurement, and speech impairment, As a result, Fetal surgery can be considered but practiced rarely when the deformity is not fatal to life, And treatment of cleft palate is performed in the form of medicine projection into uterus in animal experiments, Many studies show that growth factor and its receptor emerge from the developing palate; and the epidermal growth factor receptors have a important role in craniofacial development and in palatal fusion, The palatal morphogenesis of the avine is different from the mammal's; it takes the form of physiologic cleft palate, Recently, cleft palate fusion experiment was performed when the avine were in the period of palate formation through the exogenous TGF-β3 addition, and it showed that the exogenous TGF-β3 makes fusion of divided palate through certain process when cleft palate is occurred in palatal formation, In this study, I had the conformation of the fusion of cleft palate through the addition of TGF-β in case of chicken embryo, and observed the effect of TGF-β in EGF receptor distribution, And the following is the results of this study, 1. In case of the TGF-βl and β3 addition group, there was the decrease of EGFR(Epidermal Growth Factor Receptor) immunoreactivity in mesenchymal cells beneath the medial edge epithelium and also in epithelial mesenchymal interface which is between medial edge epithelium and nasal septum in 72 hours, 2, The immunoreactivity of the control group resembles that of normal chicken embryo palate in development, 3. In the view through fluorescence confocal microscopy, there was confluence in TGF-β3 addition group, This shows that the confluence induced by exogenous TGF-β3 is related to EGFR expression in palate of chicken embryo, which is a physiologic cleft palate model.

• BMB Reports
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• v.31 no.5
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• pp.468-474
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• 1998

Membrane depolarization in PC12 cells induces calcium influx via an L-type voltage-sensitive calcium channel (L-VSCC) and increases intracellular free calcium, which leads to tyrosine phosphorylation of epidermal growth factor (EGF) receptor and the associated adaptor protein, She. This activated EGF receptor complex then can activate mitogen-activated protein (MAP) kinase, as in nerve growth factor (NGF) receptor activation. In the present study, we investigated the role of EGF receptor in the signaling pathway initiated by membrane depolarization of PC12 cells. Prolonged membrane depolarization induced phosphorylation of extracellular signal-regulated kinase (ERK) within 1 min in undifferentiated PC12 cells. Pretreatment of PC12 cells with the calcium chelator EGTA abolished depolarization-stimulated ERK phosphorylation, but NGF-induced phosphorylation of ERK was not affected. The chronic treatment of phorbol ester, which down-regulated the activity of protein kinase C (PKC), did not affect the phosphorylation of ERK upon depolarization. In the presence of an inhibitor of EGF receptor, neither depolarization nor calcium ionophore increased the level of ERK phosphorylation. These data imply that the EGF receptor is functionally necessary to activate ERK and neurite outgrowth in response to the prolonged depolarization in PC12 cells, and also that PKC is apparently not involved in this signaling pathway.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• BMB Reports
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• v.34 no.1
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• pp.66-72
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• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Journal of Microbiology and Biotechnology
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• v.27 no.1
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• pp.72-76
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• 2017

Detection of exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene, which results in increased and sustained phosphorylation of EGFR, is important for diagnosis and treatment guidelines in non-small-cell lung cancer. Here, we have developed a simple and convenient detection system using the interaction between G-quadruplex and fluorophore thioflavin T (ThT) for discriminating EGFR exon 19 deletion mutant DNA from wild type without a label and quencher. In the presence of exon 19 deletion mutant DNA, the probe DNAs annealed to the target sequences were transformed into G-quadruplex structure. Subsequent intercalation of ThT into the G-quadruplex resulted in a light-up fluorescence signal, which reflects the amount of mutant DNA. Due to stark differences in fluorescence intensity between mutant and wild-type DNA, we suggest that the induced G-quadruplex structure in the probe DNA can report the presence of cancer-causing deletion mutant DNAs with high sensitivity.