• The Korean Journal of Medicine
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• v.99 no.2
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• pp.96-103
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• 2024

Lung cancer is the leading cause of cancer death in Republic of Korea. After their initial diagnosis, only 10-20% of patients with advanced non-small cell lung cancer (NSCLC) survive for 5 years of longer. Given enormous advances in therapeutics such as novel targeted therapies and immunotherapies, survival rates are improving for advanced patients with NSCLC; 5-year survival rates range from 15% to 50%, contingent upon the biomarker. Detection of the specific molecular alteration as biomarker is thus crucial for identifying subgroups of NSCLC that contain therpapeutically targetable oncogenic drivers. This review examines the process of diagnosing lung adenocarcinoma with dominant biomarkers in order to customize treatment with appropriate targeted therapy.

• Oncology Letters
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• v.18 no.3
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• pp.3388-3398
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• 2019

Leucine rich repeat LGI family member 3 (LGI3) is a member of the LGI protein family. Our previous studies reported that LGI3 was expressed in adipose tissues, brain and skin, where it served roles as a multifunctional cytokine and pro-inflammatory adipokine. It was hypothesized that LGI3 may be involved in cytokine networks in cancer. The present study aimed to analyze differentially expressed genes in non-small cell lung cancer (NSCLC) tissues and NSCLC cohort data, to evaluate the prognostic role of LGI3. Expression microarray and NSCLC cohort data were statistically analyzed by bioinformatic methods, and protein-protein interactions, functional enrichment and pathway, gene coexpression network (GCN) and prognostic association analyses were performed. The results demonstrated that the expression levels of LGI3 and its receptor a disintegrin and metalloproteinase domain-containing protein 22 were significantly decreased in NSCLC tissues. A total of two upregulated genes and 11 downregulated genes in NSCLC tissues were identified as LGI3-regulated genes. Protein-protein interaction network analysis demonstrated that all LGI3-regulated genes that were altered in NSCLC were involved in a protein-protein interaction network cluster. Functional enrichment, Kyoto Encyclopedia of Genes and Genomes pathway and GCN analyses demonstrated the association of these genes with the immune and inflammatory responses, angiogenesis, the tumor necrosis factor pathway, and chemokine and peroxisome proliferator-activated receptor signaling pathways. Analysis of NSCLC cohorts revealed that low expression levels of LGI3 was significantly associated with poor prognosis of NSCLC. Analysis of the somatic mutations of the LGI3 gene in NSCLC revealed that the amino acid residues altered in NSCLC included two single nucleotide polymorphism sites and three phylogenetically coevolved amino acid residues. Taken together, these results suggest that LGI3 may be a potential prognostic marker of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3249-3253
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• 2016

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

• Herbal Formula Science
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• v.21 no.1
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• pp.51-70
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• 2013

Objectives : The object of this study was to observe anticancer and related immunomodulatory effects of Insamyangyoung-tang extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of ISYYTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, which are intact control, tumor bearing control, 5-fluorouracil (FU) 30 mg/kg, ISYYTe 50 mg/kg, ISYYTe 100 mg/kg, ISYYTe 200 mg/kg, each of 8 mice per group were used in the present study. Changes on the body weight, tumor volume and weight, lymphatic organ (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Results : As results of ISYYTe 50, 100 and 200 mg/kg treatment, decreases in the tumor volumes and weights were detected. At histopathological observations, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of all three different dosages of ISYYTe. As results of tumor cell inoculation, marked decreases of spleen and popliteal lymph node weights, serum IFN-${\gamma}$, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents and splenocytes were observed with histopathological atrophic changes of spleen and popliteal lymph nodes. Conclusions : Over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in ISYYTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, there are no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1241-1247
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• 1996

From January 1989 to March 1996, we have operated on 102 cases of non-small cell lung cancer at the department of Thoracic and Cardiovascular Surgery, Yonsei University Wonju College of Medicine. They were clinically evaluated. The results are as follows; 1. The peak incidence of age of primary lung cancer was 5th decade(34.3%) and 6th decade(38.2%). Male to female ratio was 2.5:1. 2. Most of symptoms were respiratory, which were cough(61.8%), sputum(43.l%), chest discomfort and pain(30.4%), dyspnea(27.5%), and hemoptysis(9.8%). Asymptomatic cases were 1.9% of study group. 3. Methods of diagnostic confirmation were bronchoscopic biopsy(59.8%), sputum cytology(17.6%), percutaneous needle aspiration(11.8%) and open biopsy(10.8%). 4. Histopathologic classifications were squamous cell carcinoma(55.9%), adenocarcinoma(30.5%), adenosquamous cell carcinoma(6.9%), large cell carcinoma(4.9%), bronchioalveolar cell carcinoma(0.9%), and mixed cell carcinoma(0.9%). 5. Methods of operation were pneumonectony(47.1%), lobectomy(38.2%), bilobectomy(5.9%), wedge resection(1.9%), exploration(6.9%), and overall resectability was 93.1%. 6. Postoperative staging classifications were Stage I (13.7%), Stage II(31.4%), Stage IIIa(38.3%), Stage IIIb(14.7%), and Stage IV(1.9%). 7. The postoperative complications developed in 9.8%, and operative mortality was 1.9 %. 8. One year survival rate was 81.7%, 3 year 49.7% and 5 year 21.8%. According to stage, 5 year survival rate was 39% in stage I, 24.3% in stage II, 23.9% in stage IIIa.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.11 no.9
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• pp.4220-4241
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• 2017

For the downlink energy-harvesting small cell network, this paper proposes an interference management algorithm based on distributed coalitional game. The cooperative interference management problem of the energy-harvesting small cells is modeled as a coalitional game with transfer utility. Based on the energy harvesting strategy of the small cells, the time sharing mode of the small cells in the same coalition is determined, and an optimization model is constructed to maximize the total system rate of the energy-harvesting small cells. Using the distributed algorithm for coalition formation proposed in this paper, the stable coalition structure, optimal time sharing strategy and optimal power distribution are found to maximize the total utility of the small cell system. The performance of the proposed algorithm is discussed and analyzed finally, and it is proved that this algorithm can converge to a stable coalition structure with reasonable complexity. The simulations show that the total system rate of the proposed algorithm is superior to that of the non-cooperative algorithm in the case of dense deployment of small cells, and the proposed algorithm can converge quickly.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.379-388
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• 2002

Background : Although patients with stage IV non-small cell lung cancer are known to have a poor prognosis, the prognostic factors for survival have not been well evaluated. Such factors may be different from those for overall survival. This study was performed to analyze the prognostic factors for survuval and the variation of survival according to metastatic organ, in patients with stage IV non-small cell lung cancer. Materials and Methods : From January 1997 to December 2000, 151 patients with confirmed stage IV non-small cell lung cancer were enrolled into this study retrospectively. The clinical and laboratory data were analyzed using univareate Kaplan-Meied and Multivariate Cox regression models. Results : On univariate analysis, age, performance status, serum albumin level, weight loss, forced expiratory volume in one second (FEV1), systemic chemotherapy, the number of metastatic organs and serum lactate dehydrogenase (LDH) level were significant factors (p<0.05). In multivariate analysis, important factors for survival were ECOG performance (relative risk of death [RR]: 2.709), systemic chemotherapy (RR: 1.944), serum LDH level (RR: 1.819) and FEV1 (RR: 1.774) (p<0.05), Metastasis to the brain and liver was also a significant factor on univariate analysis). The presence of single lung metastasis was associated with better survival than that of other metastatic organs (p=0.000). Conclusion : We confirmed that performance status and systemic chemotherapy were independent prognostic factors, as has been recognized. The survival of stage IV non-small cell lung cancer patients was different according to the metastatic organs. Among the metastatic sites, only patients with metastasis to the lung showed bettrer survival than that of other sites, while metastasis of the brain or liver was associated with worse survival than that of other sites.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.731-736
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• 1995

Background: Surgical resection is the treatment of choice for localized, operable non-small cell carcinoma of the lung. Curative radiotherapy, however, is considered an alternative to surgery in patients with poor performance state, poor cardiopulmonary function, or who refuse surgery. However, the difference in prognosis after surgery and radiotherapy is not well established in the patients with stage I non-small cell lung cancer. Method: To evaluate the difference in progonsis between surgery and radiotherapy in stage I non-small cell lung cancer, a retrospective study was done with 15 patients treated with curative radiotherapy and 24 patients treated with curative surgery. Results: The overall response rate was 80%, with 33% complete response, after radiotherapy. The median survival time of the patients with radiotherapy was 14.9 months, with 2-year and 5-year survival rates of 22% and 0%, respectively. The median survival time of the patients with surgery was 37.7months, with 2-year and 5-year survival rates of 65% and 41%, respectively. Conclusion: These results suggest that surgery is better than the radiotherpy in view of survival rate and it is necessary to recommend, more strongly, curative surgery to patients with stage I non-small cell lung cancer if the patients are able to receive operation. To compare, more accurately, the difference in prognosis by the modality of therapy, large multicenter study is needed.

• Journal of Chest Surgery
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• v.38 no.6 s.251
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• pp.421-427
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• 2005

Complete surgical resection is the most effective treatment for pT1/2N1 non-small cell lung cancer, however 5 year survival rate of these patients is about $40\%$ and the major cause of death is recurrent disease. We intended to clarify the risk factors of recurrence in completely resected pT1/2N1 non-small cell lung cancer. Material and Method: From Jan. f990 to Jul. 2003, total of 117 patients were operated for pT1/2N1 non-small cell lung cancer. The risk of recurrence according to patients characteristics, histopathologic findings, type of resection, pattern of lymph node metastasis, postoperative adjuvant treatment were evaluated retrospectively. Result: Mean age of patients was 59.3 years. There were 14 patients with T1N1 and 103 patients with T2N1 disease. Median follow-up time was 27.5 months and overall 5 year suwival rate was $41.3\%$. 5 year freedom-from recurrence rate was $54.1\%$. Recurrence was observed in $44 (37.6\%)$ patients and distant recurrence developed in 40 patients. 5 year survival rate of patients with recurence was $3.3\%$, which was significantly lower than patients without recurrence $(61.3\%,\;p=0.000).$ In multi-variate analysis of risk factors for freedom-from recurrence rate, multi-station N1 $(hazard\;ratio=1.997,\;p=0.047)$ was a poor prognostic factor. Conclusion: Multi-station N1 is the risk factor for recurrence in completely resected pT1/2N1 non-small cell lung cancer.