• Journal of Chest Surgery
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• 제35권9호
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• pp.659-663
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• 2002

이 논문은 비소세포폐암으로 새로이 진단 받은 환자에서 수술 전 병기판정에 통상적으로 골 스캔의 유용성에 대하여 연구하였다. 대상 및 방법: 서울대병원에서 2000년 1월부터 12월까지 비소세포 폐암으로 진단 받은 환자 258명을 대상으로 하였다. 수술 전 병기는 과반수에서(132명) 수술이 불가능할 정도로 진행된 상태였다. 골 원격전이의 임상 평가 항목으로 증상, alkaline phosphatase, calcium 등을 채택하였고 모든 환자의 골 스캔 결과를 검토하여, 각각의 민감도, 특이도, 음성 예측률, 양성 예측률을 산출하였다. 최종적인 골 전이의 판단은 일반 X-lay나 MRI 또는 골 생검을 기준으로 하였다. 골 전이만 없다면 수술이 가능한 (“potentially operable”)환자 126명의 임상 경과를 따로 분석하여 수술 대상 환자에서 골 전이에 대한 임상 평가의 중요성을 검토하였다. 결과: 골 전이에 대한 골 스캔의 민감도는 96%, 특이도는 75% 양성 예측률은 44%, 음성 예측률은 99%였고, 골 스캔에 대한 임상 평가의 민감도, 특이도, 양성 예측률, 음성 예측률은 각각 54%, 73%, 54%, 72%였다. 골 전이에 대한 임상 평가의 경우는 80%, 70%, 38%, 94%였다. 골 전이만 배제하면 수술이 가능하였던 “potentially operable”군 환자 126명에서 골 전이에 대한 임상 평가의 음성 예측률은 99%였다. 결론: 폐암 진단 당시 병기 결정에 있어서, 골 전이에 대한 철저한 임상 평가가 필수적이다. 특히 골 전이 외에 다른 수술 불가능 요인이 없는 환자군에서 임상 평가 결과 특이사항이 없을 경우 골 전이의 확률이 매우 낮아, 통상적인 골 스캔 없이도 근치적 수술을 고려할 수 있음을 확인하였다. 그러나 임상 평가 결과 양성인 경우에는 약 30% 이상의 환자에서 골 전이가 발견되므로 골 전이를 발견하기 위한 골 스캔은 물론 다른 여러 가지 진단법을 적극적으로 검토해야 한다.

• 대한의생명과학회지
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• 제25권4호
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• pp.293-301
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• 2019

Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제79권2호
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• pp.85-90
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• 2016

Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

• Tuberculosis and Respiratory Diseases
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• 제77권1호
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• pp.13-17
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• 2014

Background: This study analyzed the negative prognostic factors in patients who received second-line chemotherapy for advanced inoperable non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the records of 137 patients with inoperable stage III-IV NSCLC who received second-line chemotherapy. The effects of clinical parameters on survival were analyzed and the hazard ratios (HR) for mortality were identified by a Cox regression analysis. Results: Sex, age older than 65 years, smoking history, cell type, T-stage, best response to first-line chemotherapy and first-line chemotherapy regimen were significant negative predictors in univariate analysis. The multivariate analysis showed that patients older than 65 years (HR, 1.530; 95% confidence interval [CI], 1.020-2.297), advanced T stage (T4 vs. T1; HR, 2.273; 95% CI, 1.010-5.114) and non-responders who showed progression with first-line chemotherapy (HR, 1.530; 95% CI, 1.063-2.203) had higher HR for death. Conclusion: The age factor, T stage and responsiveness to first-line chemotherapy were important factors in predicting the outcome of patients with advanced NSCLC who received second-line chemotherapy. The results may help to predict outcomes for these patients in the future.

• Journal of Applied Biological Chemistry
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• 제57권2호
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• pp.113-122
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• 2014

A5E is complex of several medicinal herb ethanol extracts. The aim of this study is investigating the anticancer effect for non-small cell lung cancer. The antitumor effects of A5E on NCI-H460 were examined by regulation of cell proliferation, apoptosis, cell cycle arrest, mitochondrial membrane potential (${\Delta}{\Psi}_m$), and apoptosis-related protein. Cell proliferation was measured by MTS assay. Apoptosis induced by A5E was confirmed by Annexin V-fluorescein isothiocyanate (FITC)/Propidium Iodide (PI) staining, and cell cycle arrest was measured by PI staining. NF-${\kappa}B$ translocation was detected by immunofluorescence and MMP (${\Delta}{\Psi}_m$) was measured by JC-1 staining. The expression of extrinsic pathway molecules such as FasL and FADD were elevated, and procaspase-8 was processed by A5E. In addition, intrinsic pathway related molecules were altered. The Bcl-2 and Bcl-xl levels decreased, Bax increased, and cytochrome C was released. In addition, the mitochondrial membrane potential collapsed, and caspase-3 and poly-(ADP-ribose) polymerase were processed by A5E. Moreover, A5E affected the cellular survival pathway involving phosphatidylinositol 3-kinase (PI3K)/Akt and NF-${\kappa}B$. PI3K and Akt were downregulated, also NF-${\kappa}B$ expression was decreased, and nuclear translocalization was inhibited by A5E. These results suggested that A5E delays proliferation, inhibit cell cycle progression and induce apoptosis in human lung cancer cell. We conclude that A5E is a potential anticancer agent for human lung carcinoma.

• Journal of Chest Surgery
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• 제29권11호
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• pp.1241-1247
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• 1996

1989년 1월부터 1996년 3월까지 연세대학교 원주의과대학 흉부외과학 교실에서 비소세포폐암으로 수술을 시행 받은 환자 102명을 대상으로 연령 및 성별 분포, 임상 증상, 진단 방법, 병리 조직 소견, 수술방법, 수술전·후의 병기, 수술후 합병증 및 사망률과 장기 생존율을 조사한 결과 다음과 같은 결론을 얻었다. 폐암 환자의 연령은 50대이후에서 가장 많은 분포를 보였으며(83.3%), 남녀 성비는 2.52:1로서 남자 환자가 많았으며, 수술전 진단은 기관지경 검사가 59.8%, 객담 세포 검사가 17.6%, 경피적 조직 검사가 11.8% 그리고 진단을 얻지 못한 경우가 10.8%이었다. 조직학적 분류는 편평상피세포암이 57례, 선암이 31례, 기관지폐포세포암이 1례, 미분화 거대세포암이 5례, 편평 상피 세포와 선암의 혼합암이 7례 였으며, 세 가지 세포형이 같이 있는 혼합암 1례가 관찰되었다. 그리고 수술 방법은 전폐 절제술이 48례로 가장 많았으며 폐엽절제술 39례, 우폐 양엽절제술이 6례, 폐설상절제술이 2례, 개흉술만 시행한 것이 7례이었다. 수술 전후의 Stage에서는 수술전 Stage I이 12.7%, II 31.4%, IIIa 47.1%, IIIb 8.8%이였으며, 수술 후에는 Stage I이 13.7%, II 31.4%, IIIa 38.3%, IIIb 14.7% 및 IV 1.9%를 차지하였으며 또한 술전·후의 병기가 달랐던 경우가 26% 였다. 그리고 수술후 합병증은 10례이었으며, 사망은 2례에서 발생하였다. 장기생존율은 추적 관찰이 가능하였던 90례를 대상으로 전체 생존율은 1년이 81.7%, 3년이 49.7%, 5년이 21.8%로 나타났으며, 병기별 5년 생존율은 병기 I 38.9%, 병기 II 24.3%, 병기 IIIa 23.9% 였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.161-166
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• 2014

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2325-2331
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• 2013

Objective: To detect effects of plumbagin on proliferation and apoptosis in non-small cell lung cancer cell lines, and investigate the underlying mechanisms. Materials and Methods: Human non-small cell lung cancer cell lines A549, H292 and H460 were treated with various concentrations of plumbagin. Cell proliferation rates was determined using both cell counting kit-8 (CCK-8) and clonogenic assays. Apoptosis was detected by annexin V/propidium iodide double-labeled flow cytometry and TUNEL assay. The levels of reactive oxygen species (ROS) were detected by flow cytometry. Activity of NF-${\kappa}B$ was examined by electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Western blotting was used to assess the expression of both NF-${\kappa}B$ regulated apoptotic-related gene and activation of p65 and $I{\kappa}B{\kappa}$. Results: Plumbagin dose-dependently inhibited proliferation of the lung cancer cells. The IC50 values of plumbagin in A549, H292, and H460 cells were 10.3 ${\mu}mol/L$, 7.3 ${\mu}mol/L$, and 6.1 ${\mu}mol/L$ for 12 hours, respectively. The compound concentration-dependently induced apoptosis of the three cell lines. Treatment with plumbagin increased the intracellular level of ROS, and inhibited the activation of NK-${\kappa}B$. In addition to inhibition of NF-${\kappa}B$/p65 nuclear translocation, the compound also suppressed the degradation of $I{\kappa}B{\kappa}$. ROS scavenger NAC highly reversed the effect of plumbagin on apoptosis and inactivation of NK-${\kappa}B$ in H460 cell line. Treatment with plumbagin also increased the activity of caspase-9 and caspase-3, downregulated the expression of Bcl-2, upregulated the expression of Bax, Bak, and CytC. Conclusions: Plumbagin inhibits cell growth and induces apoptosis in human lung cancer cells through an NF-${\kappa}B$-regulated mitochondrial-mediated pathway, involving activation of ROS.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4421-4426
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• 2013

Objective: The present study employed 5-aza-2'-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer (NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. Methods: Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR, a specific demethylating agent, for 24, 48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM) to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), real time polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 gene methylation status, mRNA expression and protein expression. Results: MTT assay showed that the growth of A549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group (0 ${\mu}mol/L$ 5-Aza-CdR). After treatment with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h, FCM showed their proportion in G0/G1 was $69.7{\pm}0.99%$, $76.1{\pm}0.83%$, $83.8{\pm}0.35%$, $95.5{\pm}0.55%$ respectively (P<0.05), and the proportion in S was $29.8{\pm}0.43%$, $23.7{\pm}0.96%$, $15.7{\pm}0.75%$, $1.73{\pm}0.45%$, respectively (P<0.05), suggesting 5-Aza-CdR treatment induced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 gene was detected in control group (0 ${\mu}mol/L$ 5-Aza-CdR), and demethylation appeared after treatment with 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were $1{\pm}0$, $1.49{\pm}0.14$, $1.86{\pm}0.09$ and $5.80{\pm}0.15$ (P<0.05) respectively. Western blotting analysis showed the relative expression levels of TFPI-2 protein were $0.12{\pm}0.01$, $0.23{\pm}0.02$, $0.31{\pm}0.02$, $0.62{\pm}0.03$ (P<0.05). TFPI-2 protein expression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration. Conclusions: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expression in the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation of TFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinical treatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be one molecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR.

• BMB Reports
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• 제47권2호
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• pp.104-109
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• 2014

FAM176A (family with sequence similarity 176 member A) is a novel molecule related to programmed cell death. A decreased expression of FAM176A has been found in several types of human tumors in including lung cancers. In the present study, we investigated the biological activities of FAM176A on the human non-small cell lung cancer cell line H1299 cells. We constructed a recombinant adenovirus 5-FAM176A vector (Ad5-FAM176A) and evaluated the expression and anti-tumor activities in vitro. Cell viability analysis revealed that the adenovirus-mediated increase of FAM176A inhibited the growth of the tumor cells in a dose- and time-dependent manner. This inhibitory effect was mediated by both autophagy and apoptosis that involved caspase activation. In addition, cell cycle analysis suggested that Ad5-FAM176A could induce cell cycle arrest at the G2/M phase, all of which suggested that adenovirus-mediated FAM176A gene transfer might present a new therapeutic approach for lung cancer treatment.