• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.8-14
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• 2014

Non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) sensitizing mutations has a distinct disease entity. Patients with this cancer have better prognosis, and frequently achieve long-term survival. EGFR-tyrosine kinase inhibitor (TKI) is the drug of choice for this cancer; but the disease inevitably progresses, after durable response. The tumor is a mixture of EGFR-TKI sensitive clones and resistant clones, regardless of their molecular mechanisms. EGFR-TKI sensitive clones are very susceptible to this drug, but rarely eradicated; so, withdrawal of the drug permits rapid regrowth of drug sensitive clones, possibly causing "disease flare." Re-administration or continuation of EGFR-TKI can effectively suppress the expansion of drug sensitive clones, even when the total tumor volume continuously increases. Chemotherapy can definitely prolong the survival of patients experiencing EGFR-TKI failure. Prospective clinical trials are warranted to compare efficacies of chemotherapeutic agents. A few retrospective studies suggested that a taxanebased regimen may be superior to others. Here, we reviewed therapeutic options and clinical evidence about this unique disease entity.

• BMB Reports
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• v.47 no.10
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• pp.581-586
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• 2014

Epidermal growth factor (EGF) is known to play key roles in skin regeneration and wound-healing. Here, we demonstrate that Pep2-YAC, a tripeptide covering residues 29-31 in the B loop of EGF, promotes the proliferation of HaCaT keratinocytes with activity comparable to EGF. The treatment of HaCaT cells with Pep2-YAC induced phosphorylation, internalization, and degradation of EGFR and organization of signaling complexes, which consist of Grb2, Gab1, SHP2, and PI3K. In addition, it stimulated the phosphorylation of ERK1/2 at Thr 202/Tyr 204 and of Akt1 at Ser 473 and the nuclear translocation of EGFR, STAT3, c-Jun, and c-Fos. These results suggest that Pep2-YAC may be useful as a therapeutic agent for skin regeneration and wound-healing as an EGFR agonist.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6619-6623
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• 2013

Background:The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing. Methods: High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients. Results: The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM. Conclusions: Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4295-4299
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• 2013

Background: Pretreatment serum p53 and epidermal growth factor receptor (EGFR) were assessed using enzyme-linked immunosorbent assay (ELISA) in patients with acute leukemia to analysis their roles in characterization of different subtypes of the disease. Materials and Methods: Serum samples from thirty two patients with acute myeloid leukemia (AML) and fourteen patients with acute lymphoid leukemia (ALL) were analysed, along with 24 from healthy individuals used as a control group. Results: The results demonstrated a significant increase of serum p53 and EGFR in patients with AML (p<0.0001) compared to the control group. Also, the results showed a significant increase of both markers in patients with ALL (p<0.05, p<0.0001 respectively). Sensitivities and specificities for these variables were 52% and 100% for p53, and 73.9%, 95.8% for EGFR. Serum p53 and EGFR could successfully differentiate between M4 and other AML subtypes, while these variables failed to discriminate among ALL subtypes. A positive significant correlation was noted between p53 and EGFR. Negative significant correlations were observed between these variables and both of hemoglobin (Hg) content and RBC count. Conclusions: Mutant p53 and EGFR are helpful serological markers for diagnosis of patients with AML or ALL and can aid in characterization of disease. Moreover, these markers may reflect carcinogenesis mechanisms.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.159-164
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• 2007

Stimulation of epidermal growth factor receptor (EGFR) is essential in signaling pathway of tumor cells. Thus, EGFR has intensely studied as an anticancer target. We developed hologram quantitative structure activity relationship (HQSAR) models for data set which consists of tricyclic azepine derivatives showing inhibitory activities for EGFR. The optimal HQSAR model was generated with fragment size of 6 to 7 while differentiating fragments having different atom and connectivity. The model showed cross-validated $q^2$ value of 0.61 and non-cross-validated $r^2$ value of 0.93. When the model was validated with an external set excluding one outlier, it gave predictive $r^2$ value of 0.43. The contribution maps generated from this model were used to interpret the atomic contribution of each atom to the overall inhibition activity. This can be used to find more efficient EGFR inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4485-4494
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• 2013

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3187-3190
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• 2013

Background: Epidermal growth factor receptor (EGFR) is a transmembrane receptor which contributes to many processes involved in cell survival, proliferation and inhibits apoptosis, that may lead to cancer development. Gastric cancer is one of the most common diseases of digestive system that has low 5-year-survival. The aim of this research was to determine the significance of EGFR tyrosine kinase domain gene polymorphisms in gastric cancer in Iran. Materials and Methods: In the present study, 83 patients with gastric cancer and 40 normal subjects were investigated for EGFR gene polymorphisms in exons 18-21 by PCR-SSCP. Then, DNA sequencing was conducted for different mobility shift bands. Finally the data were statistically analyzed using the chi-2 test and the SPSSver.16 program. Results: Exon 18 of EGFR gene showed three different bands in SSCP pattern and DNA sequencing displayed one mutation. SSCP pattern of Exons 19 and 21 did not show different migration bands. Exon 20 of EGFR gene revealed multiple migrate bands in SSCP pattern. DNA sequencing displayed 2 mutations in this exon: one mutation was caused amino acid change and another mutation was silent. Conclusion: It may be that EGFR tyrosine kinase gene polymorphisms differ between populations and screening could be useful in gastric cancer patients who might benefit from tyrosine kinase inhibitor therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.695-700
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• 2013

Background: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. Patients and Methods: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip-chemiluminescence at the corresponding time, and correlations were analyzed. Results: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. Conclusions: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.

• KSBB Journal
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• v.7 no.3
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• pp.201-208
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• 1992

Cell surface binding of epidermal growth factor(EGF) to EGF receptors was studied for a series of site-directed receptor mutants transfected into B82 mouse fibroblasts. Scatchard plots for truncation mutant receptors significantly lost nonlinearity for truncations below residue 1022. Transient plots of dissociation kinetics exhibited biphasic behavior for all receptor types, but the fraction of receptor in slow-dissociating form was reduced by an order of magnitude for the truncation mutants below residue 1022. Comparison of dissociation kinetics between control cells and cells treated with Triton X-100 revealed no significant variation for the slow-dissociating receptor form, but a noticeable variation was observed for the fast-dissociating receptor form when EGF receptors were truncated below residue 991. These results suggest that high affinity of EGF binding at cell surface depend on the EGF receptor cytoplasmic region.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.470-475
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• 2010

Calcium-channel blockers such as nifedipine could be associated with gingival overgrowth. The aim of this study was to examine the role of Paeonia lactiflora Pallas(PLP) on nifedipine-induced gingival hyperplasia along with submandibular secretory function in rats. Animals in divided groups received nifedipine (250 mg/kg) alone and in PLP(100, 200 mg/kg) in orally administration for 3 weeks. Pure submandibular saliva was collected intraorally by micropolyethylene cannula and the mandibular gingiva was examined by means of dissecting microscope for signs of redness, tickness, inflammation and exuda. Twenty-one days nifedipine treatment induced gingival hyperplasia accompanied with reduced salivary flow rate and concentrations total protein, epidermal growth factor(EGF) and calcium in comparison with normals. Co-treatment of animals with nifedifine and PLP protected from gingival hyperplasia and retained flow rate, and concentrations of total protein, EGF and calcium in normal levels.