• Journal of Chest Surgery
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• v.54 no.5
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• pp.342-347
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• 2021

Thoracic surgeons need to be aware of several important points regarding intraoperative lymph node dissection during surgery for non-small cell lung cancer with ground-glass opacities. The first point relates to the need for lymph node dissection during sublobar resection. Since even patients undergoing sublobar resection may benefit from lymph node dissection, it should be selectively performed according to adequate indications, which require further study. Second, there seems to be no difference in postoperative morbidity between systematic sampling and systematic dissection, but the survival benefit from systematic dissection remains unclear. The results of randomized controlled trials on this topic are conflicting, and their evidence is jeopardized by a high risk of bias in terms of the study design. Therefore, further randomized controlled trials with a sound design should investigate this issue. Third, more favorable survival outcomes tend to be positively associated with the number of examined lymph nodes. Minimum requirements for the number of examined lymph nodes in non-small cell lung cancer should be defined in the future. Finally, lobe-specific lymph node dissection does not have a negative prognostic impact. It should not be routinely performed, but it can be recommended in selected patients with smaller, less invasive tumors. Results from an ongoing randomized controlled trial on this topic should be awaited.

• 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.

• Journal of Chest Surgery
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• v.56 no.2
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• pp.67-74
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• 2023

Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.474-485
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• 2000

Background : Current studies on multimodal strategy for N2 non-small cell lung cancer are being high interest, have drawn much attention. N2 lung cancer, however, is composed of is divided into several sub groups with that have different prognoses. The prognostic factors still remain controversial. Methods : Between January 1990 and June 1999, 180 patients with N2 lung cancer who underwent surgical resection were investigated, excluding 10 of these for surgical mortality. All patients underwent mediastinal lymph node dissection. 20 clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Results : The overall 5-year survival rate was 20.6%. Multivariable analyses among overall patients revealed 3 significant prognostic factors : Age, Histologic type, Vascular invasion. Based on the result, 49 patients with both age more than 60 and pathologic Non-squamous cell showed a 5-year survival of 5.0%, whereas 37 patients with neither of the factors showed a 5-year survival of 56.6%(p<0.001). And 12 patients with both vascular invasion and pathologic Non-squamous cell showed a 5-year survival of 11.9%, whereas 67 patients with neither of the factors showed a 5-year survival of 33.6%(p=0.01). Conclusion : The prognosis of surgically resected N2 disease varies according to the 3 significant prognosis factors. Tumor size may be an additional influencing factor in the prognosis of N2 disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.741-746
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• 2015

Purpose: To investigate the influence of exogenous p53 upregulated modulator of apoptosis (PUMA) expression on cell proliferation and apoptosis in human non-small cell lung cancer A549 cells and transplanted tumor cell growth in nude mice. Materials and Methods: A549 cells were divided into the following groups: control, non-carrier (NC), PUMA (transfected with pCEP4-(HA) 2-PUMA plasmid), DDP ($10{\mu}g/mL$ cisplatin treatment) and PUMA+DDP (transfected with pCEP4-(HA)2-PUMA plasmid and $10{\mu}g/mL$ cisplatin treatment). The MTT method was used to detect the cell survival rate. Cell apoptosis rates were measured by flow cytometry, and PUMA, Bax and Bcl-2 protein expression levels were measured by Western blotting. Results: Compared to the control group, the PUMA, DDP and PUMA+DDP groups all had significantly decreased A549 cell proliferation (p<0.01), with the largest reduction in the PUMA+DDP group. Conversely, the apoptosis rates of the three groups were significantly increased (P<0.01), and the PUMA and DDP treatments were synergistic. Moreover, Bax protein levels significantly increased (p<0.01), while Bcl-2 protein levels significantly decreased (p<0.01). Finally, both the volume and the weights of transplanted tumors were significantly reduced (p<0.01), and the inhibition ratio of the PUMA+DDP group was significantly higher than in the single DDP or PUMA groups. Conclusions: Exogenous PUMA effectively inhibited lung cancer A549 cell proliferation and transplanted tumor growth by increasing Bax protein levels and reducing Bcl-2 protein levels.

• The Korean Journal of Nuclear Medicine
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• v.28 no.2
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• pp.186-191
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• 1994

Tc-99m MIBI, a lipophilic cation, was reported as a useful agent for localization of lung cancer. The effect of radiation therapy on the uptake of Tc-99m MIBI in lung cancer, however, was not well evaluated. The aim of the present study was to elucidate the usefulness of Tc-99m MIBI SPECT in the localization and the assessment of radiotherapy in non-small cell lung cancer. Twenty patients(19 males and 1 female, mean age 59, 16 squamous cell ca and 4 adenoca) were studied with Tc-99m MIBI SPECT before radiation therapy. Eleven patients(10 males and 1 female, mean age 59, 8 squamous cell ca and 3 adenoca) were repeated the study 1 month after the completion of radiation therapy(mean dose 6453cGy). All patients showed positive uptakes of Tc-99m MIBI in their tumors. One patient showed a hot uptake in atelectatic area. There was no difference of Tc-99m MIBI uptakes between squamous cell ca and adenoca either on planar or tomographic images. Tc-99m MIBI uptake ratios of squamous cell ca and adenoca were $1.50{\pm}0.16$ and $1.45{\pm}0.15$ on planar images, and $2.73{\pm}0.46$ and $2.54{\pm}0.37$ on tomographic images, respectively. The concordance between radiological change(chest x-ray and CT) and change of Tc-99m MIBI uptakes was 9/11 (81.8% ). In conclusion, Tc-99m MIBI SPECT was useful in the localization of tumor and the assessment of radiation therapy in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Journal of Applied Biological Chemistry
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• v.56 no.1
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• pp.37-42
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• 2013

In eukaryotes, most of the genome are transcribed, however only a small proportion of total transcripts encodes for protein, thus resulting in many of noncoding RNAs. In order to recover DNA damage including DNA double-strand breaks (DSBs) eukaryotes have evolved complex mechanisms and these are processed through coordinated mechanisms of protein sensors, transducers, and effectors including RNAs. During recent years, small RNAs have been increasingly studied and gradually considered as key regulators in various aspects of biology. Upon DNA damage, small RNAs including diRNAs (DSB induced RNA) are generated in both plant and human cell lines. Inhibition of their biogenesis has severe influence on DSB repair system.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.274-281
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• 2016

Background: Factors associated with the prognosis of patients with small cell lung cancer (SCLC) is relatively unknown, than of those with non-small cell lung cancer. This study was undertaken to identify the prognostic factors of SCLC. Methods: The medical records of 333 patients diagnosed with SCLC at tertiary hospital from January 1, 2008, to December 31, 2012 were retrospectively reviewed. Patients were categorized by age (${\leq}65$ years vs. >65 years) and by extent of disease (limited disease [LD] vs extensive disease [ED]). Overall survival and progression free survival rates were determined. Factors associated with prognosis were calculated using Cox's proportional hazard regression model. Results: Most baseline characteristics were similar in the LD and ED groups. Eastern Cooperative Oncology Group (ECOG) performance status (PS), first chemotherapy regimen, and prophylactic cranial irradiation (PCI) differed significantly in patients with LD and ED. Mean ECOG PS was significantly lower (p<0.001), first-line chemotherapy with etoposide-cisplatin was more frequent than with etoposide-carboplatin (p<0.001), and PCI was performed more frequently (p=0.019) in LD-SCLC than in ED-SCLC. Prognosis in the LD group was better in younger (${\leq}65$ years) than in older (>65 years) patients, but prognosis in the ED group was unrelated to age. Conclusion: This study showed that overall survival (OS) was significantly improved in younger than in older patients with LD-SCLC. Univariate and multivariate analyses showed that age, PCI and the sum of cycles were significant predictors of OS in patients with LD-SCLC. However, prognosis in the ED group was unrelated to age.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.255-260
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• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.