• Tuberculosis and Respiratory Diseases
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• 제71권4호
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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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• 제24권5호
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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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• 제86권1호
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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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• 제14권11호
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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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• 제77권1호
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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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• 제47권1호
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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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• 제57권2호
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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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• 제30권7호
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• pp.701-707
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• 1997

그동안 폐암의 발생에 관여하는 여러가지 유전자의 이상이 보고되어 왔으나 모든 종류의 폐암에서 보이는 비억제적 성장(unconkolle6 growth)을 대변할 수 있는 유전자적 종양 표시자(molecular tumor marker)는 보고된 바 없었다. 최근 유전자(chromosome)의 말단부에 위치한 특이한 구조인 telomere가 세포의 노화나 증식정도 (proliferative activity)에 따라 그 구조, 특히 TrAGGG 반복 구조가 변한다는 것이 알려진 바 있다. 따라서 telomere의 반복 구조를 만드는 효소인 telomerase의 활성도는 대상 세포의 증식 상황이나 증식 가능성을 나타내는 표시 자로서의 기능이 있다고 추정된다. 따라서 이는 종양의 진단은 물론 대상 환자의 향후 예후를 판 단하는 데도 좋은 지표로 이용될 수 있다. 12개의 다양한 비소세포폐암 세포주와 수술로 적출된 41명의 비세포계암 환자의 종양 조직에 대해 nROolymerase chain reaction)을 기초로 한 TRAP assay를 이용하여 telomeiase활성도를 측정하였다. 대조군으로는 동시에 적출된, 종양으로부터 가장 먼 위치의 정상 폐조직을 이용하였다. 12개 전 종양 세포주는 물론 대부분의 종양 조직(94%)에서, 성별, 연령, 세포 병리학적 subtype, 암기(stage) 등과 관련이 언이, telomerase의 활성도가 측정되었으며 정상이라고 간주된 조직에서는 5명으로 부터 채취한 조직에서만 미약하게 telomerase활성도가 관찰되었다. 예후에 연관지어 telomerase활성도의 의미는 telmerase활성도가 보이지 않는 종글이 극히 적었고 또한 추적 관찰 기간이 짧아 판정할 수 없었다. Telomere의 길이의 변화는의미를 판정키 어려웠다. 이상의 결과는 비소세포폐암에 있어 telomerase활성도의 변화가 암발생에 아주 중요한 과정일 수 있다는 추정을 가능하게 하며 telomerase활성도의 측정이 종양의 진 단에 유용하게 이용될 수 있음을 확인시켜 주는 것이라 사료된다.

• Journal of Chest Surgery
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• 제32권2호
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• pp.185-188
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• 1999

폐에 발생한 거세포암종은 대세포암의 일종의 변형으로 현미경상 전체세포중 10% 이상의 거대한 다형, 다핵의 거세포종으로 구성되어 있으며, 중성구가 종양세포내로 들어가는 세포내행동(Emperipolesis)이 특징적인 소견이다. 국소재발과 초기전이를 잘 일으키는 고도의 악성종양으로 예후는 불량하나, 수술후 보조화학요법과 방사선요법에 의해 생존률을 높일 수 있다는 보고들이 있다. 2달간의 객혈을 주소로 내원한 46세의 남자환자가 단순 흉부 X선 검사와 전산화 단층촬영상 우상엽 첨부에 5 cm크기의 종괴가 발견되었고, 수술을 위한 검사도중 관상동맥조영술상 좌전하행지에 협착소견이 보여 경피적 경혈관혈관확장술을 시행하였다. 4주후 우상엽 절제술을 시행후 병리조직상 거세포암종으로 확인되어, 보조화학요법과 방사선요법을 받았다.

• 약학회지
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• 제55권3호
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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.