• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.259-265
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• 2011

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.413-422
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• 2020

Delphinidin is a major anthocyanidin compound found in various vegetables and fruits. It has anti-oxidant, anti-inflammatory, and various other biological activities. In this study we demonstrated the anti-cancer activity of delphinidin, which was related to autophagy, in radiation-exposed non-small cell lung cancer (NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxic dose of delphinidin (5 μM) before exposure to γ-ionising radiation (IR). We found that treatment with delphinidin or IR induced NSCLC cell death in vitro; however the combination of delphinidin pre-treatment and IR was more effective than either agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethal dose. Moreover, combined treatment with delphinidin and IR, enhanced apoptotic cell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway. Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increased the expression of autophagy-induced cell death associated-protein in radiation-exposed NSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidin pre-treatment in radiation-exposed NSCLC cells. Collectively, these results show that delphinidin acts as a radiation-sensitizing agent through autophagy induction and JNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

• Tuberculosis and Respiratory Diseases
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• v.86 no.1
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• pp.1-13
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• 2023

Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.77 no.1
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• pp.34-37
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• 2014

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.

• Journal of Chest Surgery
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• v.47 no.1
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• pp.13-19
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• 2014

Background: The aim of this study is to evaluate prognostic factors for survival in pathologic stage IIIA/N2 non-small-cell lung cancer (NSCLC), to identify the prognostic significance of the metastatic patterns of mediastinal lymph nodes (MLNs) relating to survival and to recurrence and metastasis. Methods: A total of 129 patients who underwent radical resection for pathologic stage IIIA-N2 NSCLC from July 1998 to April 2011 were retrospectively reviewed. The end points of this study were rates of loco-regional recurrence and distant metastasis, and survival. Results: The overall 5-year survival rate was 47.4%. A univariate analysis showed that age, pathologic T stage, and adjuvant chemotherapy were significant prognostic factors, while in multivariate analysis, pathologic T stage and adjuvant chemotherapy were significant prognostic factors. The metastasis rate was higher in patients with multi-station N2 involvement and with more than 3 positive MLNs. Further, non-regional MLN metastasis was associated with a higher loco-regional recurrence rate. Conclusion: Pathologic T stage and adjuvant chemotherapy were independent prognostic factors for long-term survival in pathologic stage IIIA/N2 NSCLC. The recurrence and the metastasis rate were affected by the metastatic patterns of MLNs. These results may be helpful for planning postoperative therapeutic strategies and predicting outcomes.

• Journal of Chest Surgery
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• v.57 no.2
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• pp.136-144
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• 2024

Background: Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. Methods: We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. Results: The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. Conclusion: NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.701-707
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• 1997

Although many reseraches have been persued to detect the molecular tumor marker to define the cancer, ideal tumor marker which speak for the characteristics of malignancy and has high sensitivity and specificity is not known. One of the characteristics of the malignant cells is indefinite proliferative potential, in other word, immortality. The expression of telomerase and stabilization of te10meres are con omitant with the attaiunent of immortality in tumor cells; thus the measurement of telomerase activity in clinically obtained tumor samples may provide important information which would be useful as a diagnostic marker to detect immortal cancer cells. Telomerase activity was analyzed in 12 non-small cell . lung cancer cell lines and 41 primary non-small cell lung cancers with the use of a PCR-based assay. All the cell lines and the majority of tumors displayed telomerase activity, but telomerase was not detectable in most of the corresponding pathologically-normal tissues. Telomere length was not correlated with telomerase activity. The present study indicate that measurement of telomerase activity may be useful as a molecular tumor marker in non-small cell lung cancer.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.185-188
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• 1999

The pulmonary giant cell carcinoma is classified as a variant of a large cell carcinoma and is diagnosed by the minimum component of 10% huge, pleomorphic and multinucleated giant tumor cell and emperipolesis of the neutrophils into the tumor cells. This tumor is characterized by local recurrences and early metastasis with extremely short patient survival. However, there are some reports that state that the survival time was extended by the operative resection and postoperative adjuvant chemotherapy and radiotherapy. A 46-year old male was admitted with complaint of hemoptysis for 2 months. Through chest X-ray and chest CT, a 5cm sized mass was found in the apical segment of the right upper lobe. During the preoperative evaluation, stenotic lesion in the left anterior descending coronary artery was found and treated by percutaneous transarterial coronary angioplasty. Four weeks later, right upper lobectomy was performed and the mass was proven to be a giant cell carcinoma. The patient received adjuvant chemotherapy and radiotherapy.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.267-272
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• 2011

Human NK cells, identified 30 years ago based on their ability to spontaneously kill tumor cells, constitute a subset of lymphocytes, which play an important role in the first line of immune defense and the effective function of these cells are enhanced by cytokines. Lung carcinoma has been one of the most commonly diagonosed cancer as well as the leading cause of cancer death in male. Here we provide the evidence that human natural killer cells has inhibitory effects on tumor growth of human lung cancer cell NCI-H460 (non-small cell lung cancer). Enriched NK cell population was obtained by 2 weeks cultivation in interleukin-2(IL-2)-containing medium. The resulting population comprised 26% CD3$^+$ cells, 9% CD3$^+$CD4$^+$ cells, 16% CD3$^+$CD8$^+$ cells, 76% CD56$^+$ cells, 6% CD3$^+$CD56$^+$ cells and 70% CD3$^-$CD56$^+$ cells. Activated NK cells at doese of 2.5, 5, and 10 million cells per mouse inhibited 2%, 12% and 45% of NCI-H460-induced tumor growth in nude mouse xenograft assays, repectively. This result suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for lung cancer patients.