• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.3
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• pp.177-185
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• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.490-496
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• 1996

Naphtodianthrone hypericin produced a potent antitumor activity in vitro against several tumor cells. However, it did not show any cytotoxicity on normal cells such as Macaccus rheus monkey kidney cells (MA-104) and primary cultured rat hepatocytes up to $500{\mu}M$ concentration. Hypericin added to A431 human epidermoid carcinoma cell membrane inhibited the autophosphorylation of the epidermal growth factor (EGF) receptor and the tyrosine phosphorylation of RR-SRC peptide catalyzed by an EGF-receptor. Similarly, treatment of the A431 cells with hypericin inhibited the tyrosine phosphorylation of EGF-dependent endogenous EGF-receptor by western blotting analysis. Hypericin also inhibited the T cell PTK, $P56^{lck}$, in a dose-dependent fashion with an $IC_{50}=5{\mu}M$. The tyrosine phosphorylation, on RR-SRC peptide and EGF-induced receptor autophosphorylation, either in vitro or in intact cells was inhibited by hypericin at the same concentration as that in A431 cell proliferation. These data suggest that hypericin directly inhibits EGF-receptor and $P56^{lck}$ PTK activity in vitro and can mediate such action in vivo.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.21-30
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• 2003

Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

• Proceedings of the KSMRM Conference
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• 1996.10a
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• pp.65-65
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• 1996

• Molecules and Cells
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• v.45 no.11
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• pp.789-791
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• 2022

Targeting fibroblast growth factor receptors (FGFRs) has been slow compared to other targeted cancer therapies for receptor tyrosine kinases, such as epidermal growth factor receptors. The low efficacy and variable response have limited the growth of FGFR inhibitors in clinical use. Nevertheless, recent systematic and genomic approaches have identified the biological conditions for effectively targeting FGFRs and can accelerate the development of targeted drugs. Under clinical and preclinical trials, the inhibitors started fast growing furious races to target FGFRs. Finally, FGFRs will be more actionable and targetable with more precise and effective drugs at the end of the race, passing the finish line.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.125-129
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• 1997

Purpose: The aim of this study was to find correlation between the expression of epidermal growth factor receptor (EGFR) and MR findings in the brain glioma. Materials and Methods: MR features including edema, margin, necrosis, heterogeneity, hemorrhage and contrast enhancement were retrospectively analyzed with preoperative MR images in 41 patients with proven brain gliomas (8 low grade astrocytomas, 12 anaplastic astrocytomas, 21 glioblastoma multiformes). Immunohistochemical study of EGFR was done and their expressions were graded by both stained distribution and intensity. Correlation analysis between the MR features and EGFR expressions was done. Results: Peritumoral edema was correlated with both distribution (r=0.71, p=0.00) and stain intensity (r=0.69, p=0.00) of EGFR expression. Other MR features showed no statistical correlation with EGFR expression. Conclusion: MRI is useful in evaluation of brain glioma, and peritumoral edema is useful finding that suggests EGFR expression as well as malignant histopathologic grade of the tumor.

• Tuberculosis and Respiratory Diseases
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• v.74 no.3
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• pp.129-133
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• 2013

The presence of epidermal growth factor receptor (EGFR ) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.6
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• pp.793-798
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• 2006

The quality characteristics of semen are important indicators of the fertility of a boar. Development of genetic markers for the semen quality in boars will be beneficial to the improvement of porcine fertility. We investigated the relationship between the polymorphisms of epidermal growth factor (EGF), prostaglandin-endoperoxide synthase 2 (PTGS2) and prolactin receptor (PRLR) genes, and semen quality traits in boars. The genomic DNA of 233 boars (157 Duroc and 86 Landrace) from a central testing station was subjected to genotyping for surveying gene frequency. The EGF, PTGS2 and PRLR genotypes were determined using the restriction fragment length polymorphism method. Thirty-seven normal, mature Duroc boars from an AI center were also genotyped and their semen quality traits were collected. The effect of genotype on semen quality traits was analyzed by the least-squares means method using data corrected for season. The frequencies of the AA genotype of EGF, PTGS2 and PRLR in Duroc boars were 0.14, 0.01 and 0.66, respectively. In Landrace, the frequencies of the AA genotype were 0.03, 0.09 and 0.62, respectively. Boars with the BB genotype in EGF, with the AB genotype in PTGS2 and with the AA genotype in PRLR had significantly better semen quality with a higher percentage of normal sperm and a lower percentage of immature sperm than those with other genotypes. These findings imply that polymorphisms of EGF, PTGS2 and PRLR genes might be used as markers for improving the semen quality of boars.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2879-2883
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• 2013

Objective: To investigate differences in mutations of epidermal growth factor receptor (EGFR) gene and relationships with clinicopathological features in patients with non-small cell lung cancer (NSCLC) between Uygur and Han ethnic groups. Methods: The Scorpions amplification refractory mutation system (Scorpions ARMS) was used to measure mutations in exons 18, 19, 20 and 21 of the EGFR gene in paraffin-embedded tumor tissue from NSCLC cases, and statistical analysis was performed to investigate links with clinicopathological features in different histological types of NSCLC. Results: Results from ARMS testing showed EGFR mutations in tumor tissues from six (6) of 50 NSCLC patients of Uygur ethnic group, with a positive rate of 12.0%; four of them (4) had exon 19 deletion in EGFR, and two (2) had L858R point mutation in exon 21 of EGFR. Statistically significant difference was noted in EGFR genetic mutation between adenocarcinoma and non-adenocarcinoma (P < 0.05), but no differences with gender, age group, smoking status, or stage (P > 0.05). EGFR mutations were detected in tumor tissues from 27 of 49 NSCLC patients of Han ethnic group, with a positive rate of 55.1%; 19 of them had exon 19 deletions, seven (7) had L858R point mutations in exon 21 of EGFR and one (1) had mutations in both exon 18 G719X and exon 20 T790M of EGFR. Statistically significant differences were noted in EGFR genetic mutations between genders and between adenocarcinoma and non-adenocarcinoma (P<0.05), but not with age group, smoking status, or stage (P > 0.05). Conclusion: Statistically significant differences were noted in the positive rates of EGFR genetic mutations in NSCLC patients between Uygur and Han ethnic groups, with lower positive rates for the Uygur cases.

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.