• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.271-278
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• 2010

Background: Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability. Methods: A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis. Results: The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group. Conclusion: EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5177-5182
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• 2012

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

• Molecules and Cells
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• v.42 no.3
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• pp.270-283
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• 2019

This study was aimed to explore if lncRNA MALAT1 would modify chemo-resistance of non-small cell lung cancer (NSCLC) cells by regulating miR-197-3p and p120 catenin (p120-ctn). Within this investigation, we totally recruited 326 lung cancer patients, and purchased 4 NSCLC cell lines of A549, H1299, SPC-A-1 and H460. Moreover, cisplatin, adriamycin, gefitinib and paclitaxel were arranged as chemotherapies, and half maximal inhibitory concentration (IC50) values were calculated to evaluate the chemo-resistance of the cells. Furthermore, mice models of NSCLC were also established to assess the impacts of MALAT1, miR-197-3p and p120-ctn on tumor growth. Our results indicated that MALAT1 and miR-197-3p were both over-expressed within NSCLC tissues and cells, when compared with normal tissues and cells (P < 0.05). The A549, H460, SPC-A-1 and SPC-A-1 displayed maximum resistances to cisplatin ($IC50=15.70{\mu}g/ml$), adriamycin ($IC50=5.58{\mu}g/ml$), gefitinib ($96.82{\mu}mol/L$) and paclitaxel (141.97 nmol/L). Over-expression of MALAT1 and miR-197-3p, or under-expression of p120-ctn were associated with promoted viability and growth of the cancer cells (P < 0.05), and they could significantly strengthen the chemo-resistance of cancer cells (P < 0.05). MALAT1 Wt or p120-ctn Wt co-transfected with miR-197-3p mimic was observed with significantly reduced luciferase activity within NSCLC cells (P < 0.05). Finally, the NSCLC mice models were observed with larger tumor size and weight under circumstances of over-expressed MALAT1 and miR-197-3p, or under-expressed p120-ctn (P < 0.05). In conclusion, MALAT1 could alter chemo-resistance of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.

• Analytical Science and Technology
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• v.22 no.6
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• pp.498-503
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• 2009

Lung cancer is the main cancer on the world today, due to the high case fatality. Lung cancer can devide into two major types, such as small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Mutations in the epidermal growth factor receptor (EGFR) have been described in patients with advanced NSCLC. Mutations in the EGFR are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Thus, the detection of EGFR mutation can offer an effective information in clinical decision-making. In this study, We developed very simple, cheep and rapid mutation detection system by chip-based isothermal amplification method. The method described here has shown the advantages of rapid amplification, high sensitivity, and specificity. Also, it will be useful for rapid and reliable clinical diagnosis of EGFR mutation.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.185-191
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• 2008

While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

• BMB Reports
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• v.51 no.1
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• pp.27-32
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• 2018

Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.382-386
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• 2007

Paraneoplastic limbic encephalitis is a rare disorder that is characterized by personality changes, irritability, depression, seizures, memory loss and dementia, and is commonly associated with small cell lung cancer. The cause is unknown but it is believed to be an autoimmune disorder that develops secondary to a carcinomatous process. We report a patient with the clinical feature consistent with limbic encephalitis. A 64-year-old women developed disorientation, memory loss and general weakness. She was diagnosed with NSCLC (adenocarcinoma) with a brain metastasis 1 year earlier and was treated with radiation and chemotherapy. Although the lung mass and brain metastatic lesions had improved, the brain T2-weighted MRI showed high signal intensity in the right temporal region. This lesion consisted of with limbic encephalitis and was negative to the other viral and immune markers. The patient's symptoms did not improve after steroid treatment. Our case demonstrated that a NSCLC (adenocarcinoma) also can be associated with paraneoplastic limbic encephalitis.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.431-435
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• 2014

A fifty-year-old female non-smoker with no other specific medical history visited our institute. She complained of axial back pain with no other neurological deficit. Chest X-ray, chest computed tomography (CT) scan, CT-guided needle aspiration biopsy, whole-body positron emission tomography, spine CT and spine magnetic resonance image findings suggested NSCLC with epidermal growth factor receptor (EGFR) mutation, multiple brain metastases, and two isolated metastases to the T3 and L3 vertebral bodies. She underwent chemotherapy with gefitinib ($Iressa^{TM}$) for NSCLC and gamma knife surgery for multiple brain metastases. We performed a two-staged, total en bloc spondylectomy of the T3 and L3 vertebral bodies based on several good prognostic characteristics, such as the lack of metastases to the appendicular bone, good preoperative performance status, and being an excellent responder (Asian, never-smoker and adenocarcinoma histology) to EGFR inhibitors. Improved axial back pain after the surgery enabled her to walk with the aid of a thoracolumbosacral orthosis brace on the third postoperative day. Her Karnofsky performance status score (KPS) was 90 at the time of discharge and has been maintained to date 3 years after surgery. In selected NSCLC patients with good prognostic characteristics, we suggest that locally curative treatment such as total en bloc spondylectomy or radiosurgery should be emphasized to achieve longer term survival for the selected cases.

• 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.

• CELLMED
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• v.3 no.2
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• pp.10.1-10.8
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• 2013

Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.