• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10875-10878
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• 2015

The epidermal growth factor receptor (EGFR) is an important surface receptor with N-glycans in its extracellular domain, whose glycosylation is essential for its function, especially in tumor cells. Here, we demonstrated that polylactosamine is markedly increased in H7721 hepatocellular carcinoma cells after treatment with EGF, while it apparently declined after exposure to all-trans retinoic acid (ATRA). In the study of the enzymatic mechanism of this phenomenon, we explored changes in the expression of poly-N-acetyllactosamine (PLN) branching glycosyltransferases using RT-PCR. Among the four glycosyltransferases with altered expression, GnT-V was most elevated by EGF, while GnT-V and B3GNT2 were most declined by ATRA. Next, we conducted co-immunoprecipitation experiments to test whether B3GNT2 and EGFR associate with each other. We observed that EGFR is a B3GNT2-targeting protein in H7721 cells. Taken together, these findings indicated that the altered expression of B3GNT2 will remodel the PLN stucture of EGFR in H7721 cells, which may modify downstream signal transduction.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5889-5893
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• 2014

Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.

• Tuberculosis and Respiratory Diseases
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• 제71권4호
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• pp.286-290
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• 2011

Although failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) is generally believed to be associated with cross-resistance to other EGFR TKI, the benefit of administering erlotinib as a second EGFR TKI after resistance of gefitinib as the first TKI has been well known. However, good response to gefitinib after an initial response to erlotinib has been rare. We report that a 45-year-old woman (never smoked), with lung adenocarcinoma and EGFR mutation, showed an initial response to erlotinib, and then responded to gefitinib again.

• 대한수의학회지
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• 제43권2호
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• pp.211-218
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• 2003

Human ovarian cancerous cells survive in a way that they trigger the nucleotide excision repair (NER) or double-strand DNA repair (dsDNA) repair mechanism to show resistance to anticancer drugs and activate many kinds of repair protein, thus removing damaged DNAs. Two experiments on the PA-1 human ovarian teratocareinoma cell line that hardly has any expression of epidermal growth factor receptor (EGFR) were conducted in the study; first, EGF-R was transfected and its receptor was obtained. The receptor was investigated in terms of its mutual relations with many kinds of protein concerning NER or dsDNA repair. Second, it was examined what kind impact cisplatin and adriamycin had on the effects of EGF-R over the PA-1 cell line lacking EGF-R. When being administered with cisplatin and adriamycin, Hey and Hey C2 cell lines showed a high level of resistance while PA-1 cell line a high level of sensitivity. Hey and Hey C2 cell lines that are resistant against anticancer drugs exhibited a high level of EGF-R expression while PA-1 cell line that is sensitive to them did a much lower level of the expression. When PA-1 cell line was transfected for the expression of DNA adduct and EGF-R, it showed a higher level of resistance compared to the control group. There was no difference in the expression of DNA repair proteins (DNA- dependent protein kinase, Ku70, and Ku80) between Hey and the PA-1 cell lines. The results indicate that the Hey cell line that is resistant against cisplatin and adriamycin works along the signaling system responding to the changes of EGF-R while the PA-1 cell line that is sensitive to both of them does to the lack of EGF-R.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Radiation Oncology Journal
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• 제22권2호
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• pp.77-90
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• 2004

종양 발생 과정에 관여되고 있는 분자 생물학적 기전을 직접 공격해 보자고 하는 치료 방침은 암 치료에 있어서 아주 유망한 치료방법의 하나로 인정되고 있다. Epidermal growth factor receptor (EGFR) 수용체에 여러 ligands가 결합하게 되면 발암 단계에서부터 암의 진행 과정과 전이 과정 그리고 방사선에 대한 저항성과 관련된 여러 가지중요한 신호전달체계를 활성화시킨다. 특히 진행된 두경부 암 환자들에서 EGFR이 과발현 된 경우에는 매우 불량한 예후를 나타내고 있기 때문에 이러한 signaling pathway의 selective targeting을 위한 많은 임상 시도가 이루어지고 있다. 현재까지 알려진 표적치료 항암제로는 크게 EGFR에 대한 monoclonal antibody와 tyrosin kinase Inhibitors로 대별될 수 있는데 이와 같은 약제들은 여러 xenograft에서 고무적인 실험 결과들이 입증되어 곧 바로 임상 현장에서 적용되고 있다. 그러나 기대와는 달리 EGFR Inhibitor 단독으로 치료한 초기 임상연구 결과들을 보면 극히 소수의 환자에서만 미미한 효과를 나타내고 있고, 방사선 치료와의 병용치료에서도 괄목할만한 항암 효과를 보여주지 않고 있다. 그럼에도 불구하고 많은 실험적 데이터로부터 여러 가지 생물학적 이점이 밝혀져 있고 또 미래 지향적인 치료법의 하나로 각광을 받고 있기 때문에 현재 많은 연구자들은 어떤 환자 군에서 이러한 표적 치료가 도움이 될 것이며, 방사선 치료 또는 항암 치료와는 어떤 방식으로 조합할 것인지, 또 그 순서는 어떻게 할 것이며, 또 환자 선정에 있어 reliable marker는 무엇인지, 어떻게 체내에서 신호 전달체계의 효과적인 차단을 확인할 수 있겠는지, 또한 multiple targ리ed therapy가 필 요하도록 하는 targeted agent에 대 한 Intrinsic 또는 acquired resistance의 기전은 무엇인지 등등, 현재 당면하고 있는 많은 문제점을 규명하고자 노력하고 있다. 특히 EGFR-signaling pathway를 표적으로 하는 표적 지향적 방사선 치료를 위한 translation research의 적절한 모델이 되고 있는 두경부 암 환자에서 이러한 제반 문제점을 해결하기 위해서는 더 많은 임상 연구와 함께 well-Integrated laboratory clinical research program이 필요할 것으로 생각된다 또한 EGFR antagonist 외에도 anglogenlc pathway나 cell-cycle pathway를 표적으로 하는 새로운 약제들이 계속 개발되고 있고 이에 관한 연구가 활발히 진행 중이다. 따라서 이 고찰에서는 두경부 암 환자에서 이러한 약제들을 방사선 치료와 병용하였을 때의 임상 연구 결과들을 재검토해 보고 부가적으로 EGFR blockade에 따르는 내성 문제 그리고 방사선 치료를 병용하면서 여러 표적을 동시에 차단시키는 multiple-targeted therapy의 개발 현황을 간략히 소개하고자 한다

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7885-7889
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• 2014

Background: Activating mutations of epidermal growth factor receptor (EGFR) could predict response to tyrosine kinase inhibitor (TKI) treatment in patients with non-small cell lung cancer (NSCLC). However, the detection of EGFR mutation is frequently challenging in clinical practice for the lack of tumor tissue. The aim of this study was to investigate the feasibility of performing EGFR mutation testing on various types of liquid-based cytology (LBC) samples. Materials and Methods: A total of 434 liquid-based cytology samples were collected from March 2010 and November 2013. Among them, 101 with diagnosis of lung adenocarcinoma had paired surgically resected specimens. The ADx Amplification Refractory Mutation System (ADx-ARMS) was used to determine EGFR mutation status both in LBC and resected samples. Results: All liquid-based cytology samples were adequate for EGFR mutation analysis. The mutation rate was 50.5% in the 434 NSCLC patients with LBC samples and the incidence rates of EGFR mutation were consistent among different specimens. We also detected EGFR positives in 52.5% (53/101) patients with paired histologic specimens. The concordance rate of EGFR mutation between LBC samples and paired histologic specimens was 92.1%. Conclusions: Our results suggest that liquid-based cytology samples are highly reliable for EGFR mutation testing in patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3451-3455
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• 2014

Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4205-4208
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• 2016

Background: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM). Materials and Methods: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong). Results: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months). Conclusions: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.

• Journal of Chest Surgery
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• 제31권4호
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• pp.362-368
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• 1998

편평세포폐암 환자 혈청내 SCC항원(squamous cell carcinoma antigen)의 암표지자로서의 유용성을 검정하고 암종이 성장함으로써 정상조직으로 침범하는 기전을 규명하기 위하여 폐암수술후 절제해 낸 폐암조직의 중심부와 말초부 그리고 암세포가 없는 정상 폐조직을 채취하여 SCC항원 농도와 DNA합성을 통해 세포성장과 분화에 관련이 있는 것으로 알려진 EGFr(epidermal growth factor receptor)의 농도를 측정하였다. 편평세포폐암종 조직내 SCC항원의 농도는 69＋25 ng/ml로 정상 폐조직 34＋7 ng/ml, 폐선암 35＋25 ng/ml보다 높았으며(p<0.05), EGFr의 농도는 폐암조직, 즉 편평세포암 47＋6 pmol/min, 선암 69＋20 pmol/min으로 정상 폐조직 34＋5 pmol/min, 39＋8 pmol/min보다 각각 높게는 나타났으나 유의성은 없었다. 암종의 크기에 따른 부위별 SCC항원의 농도는 암종이 직경이 3cm이하인 경우는 암종의 중심부(100＋82 ng/ml)가 말초부(55＋24 ng/ml)보다 높게 나타났으나(p>0.05), 5cm이상인 경우는 암종의 말초부(324＋92 ng/ml)가 중심부(34＋18 ng/ml)보다 현저히 높았다.(p<0.05) 그러나 부위별 EGFr의 농도는 암종의 크기에 따라 차이가 없었다. 암병기에 따른 부위별 SCC항원의 농도는 암중심부에서는 1, 2병기에서 3, 4병기로 암병기가 높아짐에 따라 감소하는 경향을 보였으나 통계적 유의성은 없었고(p>0.05), 암말초부에서는 1, 2병기 68＋37 ng/ml, 87＋35 ng/ml에서 3,4병기414＋87 ng/ml, 473＋226 ng/ml로 병기가 높아짐에 따라 현저하게 증가하였다.(p<0.05) 그러나 EGFr은 암중심부에서 1병기에서 2, 3, 4병기로 병기가 높아짐에 따라 증가하는 경향을 보였으나 통계적 유의성이 없었고(p<0.05), 암말초부에서는 병기에 따른 농도의 특이한 변화를 관찰할 수 없었다. 이상의 결과로 편평세포폐암종 조직내 SCC항원의 농도는 정상 폐조직이나 폐선암조직에서 보다 높게 나타나 혈청내 SCC항원의 농도가 편평세포폐암의 진단 및 치료효과를 예측하는데 유용한 암표지자로 생각되나, 암종내 부위별 SCC항원의 농도와 EGFr의 농도가 일치하지 않음으로써 암종이 성장함으로써 주위조직으로의 침범과 SCC항원의 농도와의 관계에 대해서는 보다 더 많은 연구가 필요할 것으로 사료된다.