• Journal of the korean academy of Pediatric Dentistry
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• 제34권3호
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• pp.438-446
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• 2007

Viable cells of periodontal ligament would be an important factor for the successful replantation of an avulsed tooth. Therefore, it is critical to choose the storage medium for the preservation of traumatically avulsed teeth. Growth factors and hormones could be considered for the therapeutic application of the maintenance of viable periodontal ligament fibroblasts (PDLFs). Epidermal growth factor (EGF) has been suggested as an important player for the regeneration and wound healing process on other tissues. Therefore, EGF was evaluated for the therapeutic application on avulsed teeth. In addition, the synergic effect of EGF with tri-iodothyronine (T3) and heparin-binding epidermal growth factor-like growth factor (HB-EGF). The cell proliferation of PDLFs was determined by MTT assay and increased dose-dependently up to 10 ng/ml in the presence of EGF. Maximum cellular growth was shown at the concentration of 10 ng/ml EGF. Also, EGF promoted the wound healing of PDLFs examined by in vitro wound healing assay. Combined effects of EGF with T3 or HB-EGF on the proliferation of PDLFs were also studied. Interestingly, EGF showed the synergic effect on the proliferation of PDLFs with T3 and HB-EGF. To find out the mechanism of the synergic effect of EGF and T3, the effect of T3 on the expression of endogenous EGF receptor was determined by RT-PCR. The result was that T3 enhanced the expression of EGF receptor in PDLFs. It suggested that EGF might be a good choice for a therapeutic application, which can be used as combination with T3 and HB-EGF.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5647-5654
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• 2015

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

• Biomedical Science Letters
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• 제8권4호
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• pp.229-234
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• 2002

Chlorella is rich in chlorella growth factor (CGF). A review of the literature has described that CGF improves the capability of a Th1-based immunity, anticancer, antioxidant antibacterial activity, growth promotion, wound healing and so on, but has not studied the effect for the metabolism and the proliferation of human skin keratinocyte. The aim of this study was to examine the effect of metabolism and the proliferation of human skin keratinocyte in vitro. CGF was extracted with an autoclaving method which is a modified hot-water extraction method from dried chlorella and conformed by means of absorbance 0.22 at 260 nm. We have measured the extracellular acidification rate (ECAR) of the CGF by Cytosensor$^{\circledR}$ Microphysiometer and evaluated responsiveness depending upon the dosage on the HaCaT cell. The ECAR for the concentrations of 0.15, 1.5, 15, 150 $\mu\textrm{g}$/ml of CGF increased as a 103.6, 128.2, 149.0 and 423.9%, respectively compared to control (0.0 $\mu\textrm{g}$/ml, 100% ECAR). The ECAR for ErbBl tyrosine kinase inhibited by 4-anilinoquinazolines, $C_{16}$H$_{14}$BrN$_3$O$_2$.HCl on tile HaCaT cells with the amounts of 10 $\mu\textrm{g}$/ml of the CCF compared with 100 $\mu\textrm{g}$/ml of rhEGF. The conclusion of the study is that CGF might increase human epidermal keratinocyte proliferation through the interaction between the epidermal growth factor receptor and itself.

• Journal of the Korea Society of Computer and Information
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• 제21권9호
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• pp.101-106
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• 2016

The epidermal growth factor receptor(EGFR) protein kinase signaling is an important pathway in cancer development and recently reported that EGFR and its kinase domain molecules are mutated in various of cancers including head and neck cancer. Functional deregulation of EGFR due to mutations in coding exons and copy number amplification is the most common event in cancers, especially among receptor tyrosine kinases(TK). We have analyzed Korean oral squamous cell carcinomas (OSCC) cell lines for mutations in EGFRTK. Exons encoding the hot-spot regions in the TK domain of EGFR (exons 17 to 23) were amplified by using polymerase chain reaction(PCR) and sequenced directly. EGFR expression was also analyzed in 8 OSCC cell lines using western blotting. Data analysis of the EGFR exons 17 to 23 coding sequences did not show any mutations in the 8 OSCC cell lines that were analyzed. The absence of mutations indicate that protein overexpression might be responsible for activation rather than mutation.

• Radiation Oncology Journal
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• 제34권1호
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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.

• BMB Reports
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• 제48권6호
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• pp.342-347
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• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• BMB Reports
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• 제32권1호
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• pp.28-32
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• 1999

Annexin I (also called lipocortin 1), a 37-kDa member of the annexin family of proteins, has been implicated in the mitogenic signal transduction by epidermal growth factor (EGF). Annexin I is phosphorylated by the EGF signal, however, the role of annexin I in the EGF signal transduction is still unknown. To transduce extracellular signals into the intracellular targets, selective translocation of the signaling molecules to their targets would be necessary. In this study, we examined the subcellular locations of annexin I during EGF signal transduction. Treatment of A549 cells with EGF resulted in the translocation of cytoplasmic annexin I to the nucleus and perinuclear region as determined by Western blot and immunofluorescent staining. The nuclear translocation of annexin I was inhibited by tyrphostin AG 1478 and genistein, the inhibitors of EGF receptor kinase and downstream tyrosine kineses, respectively. Pretreatment of cells with cyclohexamide did not inhibit the nuclear translocation. The results suggest that nuclear translocation of annexin I is controlled by a series of kinase dependent events in the EGF receptor signaling pathway and may be important in tranducing the signals by EGF.

• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.204-209
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• 2018

Purpose: Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD. Methods: Fibroblast cultures were developed from gingival biopsies of 1 GHTD patient and 1 control. The protein expression and the cellular localization of p21/CIP1/WAF1 was studied by Western immunoblotting and immunofluorescence, respectively: at the basal state and after induction with $200-{\mu}g/L$ human GH (hGH) (GH200), either with or without siRNA CIS (siCIS); at the basal state and after inductions with $200-{\mu}g/L$ hGH (GH200), $1,000-{\mu}g/L$ hGH (GH1000) or 50-ng/mL EGF. Results: After GH200/siCIS, the protein expression and nuclear localization of p21 were reduced in the patient. After successful induction of GH signaling (control, GH200; patient, GH1000), the protein expression and nuclear localization of p21 were reduced. After induction with EGF, p21 translocated to the cytoplasm in the control, whereas in the GHTD patient it remained located in the nucleus. Conclusion: In the GHTD fibroblasts, when CIS is reduced, either after siCIS or after a higher dose of hGH (GH1000), p21's antiproliferative effect (nuclear localization) is also reduced and GH signaling is activated. There also appears to be a positive relationship between the 2 inhibitors of GH signaling, CIS and p21. Finally, in GHTD, p21 seems to participate in the regulation of both the GH and EGF/EGFR pathways, depending upon its cellular location.

• Clinical and Experimental Reproductive Medicine
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• 제18권2호
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• pp.181-187
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• 1991

Epidermal growth facter(EGF)는 내열성이 강하고 분자량이 6045 dalton인 단쇄상의 polypeptide로써, Cohen에 의해 생쥐의 악하선에서 처음 발견된 이래, 여러학자들에 의해 많은 연구가 되어왔다. 인체의 EGF는 urogastrone이라고도 불리우며, 인체의 소변에서 처음 검출되었고 분자구조 및 생리작용이 생쥐의 EGF와 매우 유사한 것으로 판명되었다. EGF의 자세한 작용기전은 확실히 규명되어있지는 않지만 세포의 증식과 분화를 촉진시키며 위산의 분비를 억제시킨다고 알려져 있다. 또한 EGF receptor는 분자량이 170,000${\sim}$180,000dalton인 세포표면의 polypeptide로써 인체, 쥐, 닭, 소 등의 세포막조직에 특이하게 결합되어 있다. 최근 수년동안 몇몇 학자들에 의해 EGF가 배아와 태아 및 태반의 성장을 촉진시키고 chorionic gonadotrophin과 placental lactogen의 분비를 증진하는데 기여할 것이라고 가정되어 왔다. 그러나 아직까지 배아착상에 대한 EGF의 작용여부에 관해서는 발표된 문헌이 없어 저자는 radioreceptor assay를 이용하여 EGF receptor binding과 토끼의 배아착상과의 관계를 규명하고자 임신경과에 따른 착상부위와 비착상부위의 자궁 및 태아측 태반과 모체측 태반을 분리취득하고 receptor binding assay를 시행하여 다음과 같은 결론을 얻었다. 1. 전임신군과 비임신군의 자궁조직의 membrane fraction으로부터 specific한 EGF receptor binding이 관찰되었다. 2. 착상전 임신 3일에 자궁조직의 EGF receptor수는 4.72 +0.16($10\;mol/{\mu}g$)로 비임신시보다 의의있게 증가되어 있었고(p<0.01), 착상시기인 임신 7일에는 착상된 부위에서 20.33+6.58로 훨씬 더 높은 측정치를 나타내었다(p<0.05). 3. 착상이후 가장 먼저 취득된 임신 14일의 태아측 태반은 모체측 태반의 1.39+0.49에 비해 훨씬 높은 11.94+1.97의 EGF receptor 측정치를 보였다 (p<0.01). 4. 이상의 소견들로 보아 EGF가 토끼의 배아착상에 밀접한 관련이 있을 것으로 추측되며, 이러한 착상전후의 EGF의 작용은 태아측으로부터 일 것으로 예상된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권2호
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• pp.154-163
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• 2000

Growth factors and the receptors play an important role in the regulation of the growth and development of mammalian cells. In particular, epidermal growth factor is a polypeptide with potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(EGFR). EGFR has been described as a parameter of poor prognosis in many human neoplasms such as breast, bladder, and vulvar cancers. The objectives of this study are the evaluation of the expression of EGFR and cell cycle analysis in the head and neck squamous cell carcinomas(SCC), and the evaluation of the correlation between clinico-patholgic features and expression of EGFR and S-phase fraction. 37 head and neck squamous cell carcinoma specimens were evaluated for expression of EGFR by Western blot analysis and S-phase fraction by cell cycle analysis using the flow cytometry. The obtained results were as follows : 1. The expressions of EGFR were observed in 20 specimens(54%) among 37 head and neck SCC specimens. In case of oral SCC, 15 specimens(56%) out of 27 specimens were observed, and in case of nasopharyngeal SCC 5 specimens(50%) out of 10 specimens. 2. There was no correlation between clinical features(location, stage) of head and neck SCC and expression of EGFR (p>0.05). 3. There was a significant correlation between histo-pathological differentiation of head and neck SCC and expression of EGFR (p<0.02). 4. There was a significant correlation between expression of EGFR and S-phase fraction of cell cycle in the head and neck SCC (p<0.05). The above results suggest that expression of EGFR and S-phase fraction of cell cycle are adjunctive prognostic marker in the head and neck squamous cell carcinomas.