• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.466-473
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• 2000

Background : Patients with locally advanced non-small cell lung cancer are often treated with radiation alone or in combination with chemotherapy. Both modalities have a potentially damaging effect on pulmonary function. In order to examine changes in the cardiopulmonary exercise function of patients with locally advanced non-small cell lung cancer before and after conventional radiotherapy, we conducted a prospective study involving patients with such cancer, that had received radiation therapy. Method : Resting pulmonary function test, thoracic radiographic finding and cardiopulmonary exercise test(CPET) were assessed prior to and 4 weeks following radiation therapy in 11 male patients with locally advanced non-small cell lung cancer. Patient with endobronchial mass were excluded. Results : The forces vital capacity (FVC), forced expiratory volume in 1 second ($FEV_1$ and maximal voluntary ventilation (MVV) did not decreased between before and 4 weeks after radiation but the diffusing capacity (DLCO) had decreased by 11% 4 weeks after radiation, which was not statistically significant. No changes in maximal oxygen consumption ($VO_2$max), carbon dioxide production ($VCO_2$), exercise time and work load were attributed to radiation therapy. Follow up cardiopulmonary exercise testing revealed unchanged cardiovascular function, ventilatory function and gas exchange. No difference in cardiopulmonary exercise test performance was observed between pre- and post-radiation. Conclusion : Cardiopulmonary exercise function did not decrease within the short-term after the radiation of patients with locally advanced non-small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2413-2419
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• 2013

Background: Use of epidermal growth factor receptor inhibitors (EGFR-TKIs ) is now standard for non-small-cell lung cancer (NSCLC). However, the effects of EGFR-TKIs in maintenance therapy for advanced NSCLC patients are still unclear. The preent meta-analysis was performed to examine pooled data of randomized control trials (RCT) where EGFR-TKIs were compared against placebo in maintenance regimens for patients with advanced NCSLC to quantify potential benefits and determine safety. Methods: Several data bases were searched, including PubMed, EMBASE and CENTRAL, and we performed an internet search of conference literature. The endpoints were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of the published data, using Comprehensive Meta Analysis software (Version 2.0). with a fixed effects model and an additional random effects model, when applicable. The results of the meta-analysis are expressed as hazard ratios (HRs) or risk ratios (RRs), with their corresponding 95% confidence intervals (95%CIs). Results: The final analysis included six trials, covering 3,758 patients. Compared with placebo, EGFR-TKIs maintenance therapy improved ORR and PFS for patients with advanced NSCLC, the difference being statistically significant (P<0.05), but proved unable to prolong patients' OS. The main adverse reactions were diarrhea and rashes. Conclusion: EGFR-TKIs demonstrated encouraging efficacy, safety and survival when delivered as maintenance therapy for patients with advanced NSCLC after first-line chemotherapy, especially for the patients who had adenocarcinomas, were female, non-smokers and patients with EGFR gene mutations.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.259-263
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• 2016

Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4703-4706
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• 2012

Objective: To compare efficacy and safety profile of vinorelbine, ifosfamide and cisplatin (NIP) with etoposide and cisplatin (EP) in the treatment of advanced combined small cell lung cancer (c-SCLC). Methods: From January 2006 to December 2010, 176 patients with advanced c-SCLC were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were progression free survival (PFS), response rate (RR) and toxicity. Results: Overall RR was 30.0% in the NIP and 38.5% in the EP group; there was no significant difference (P=0.236). The PFS in the EP group was little longer than that of NIP group, with 6.5 months for EP and 6.0 months for NIP group, but the difference was statistically non-significant (P=0.163). The median OS and one year survival rates were 10.4 months and 36.3% for NIP group, and 10.8 months and 49.0% for EP respectively, EP showing a survival benefit, although this was not statistically significant. Both groups well tolerated the adverse effects. The incidence of grade I-II leucopenia and alopecia in the NIP group was significantly higher than that of EP group (32.5% vs. 10.4% (P<0.001, 35.0% vs. 12.5%, P<0.001). Conclusion: the ORR, PFS and OS in NIP were slightly inferior to traditional regimen EP. The toxicity of NIP can be considered tolerable. The usage of three drugs combination in the treatment of mixed SCLC remains uncertain. Nevertheless, the results need to be further confirmed by large, prospective clinical trials.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.4
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• pp.117-123
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• 2021

Gefitinib, a first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), provides obvious clinical benefit in patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, patients ultimately develop gefitinib resistance which mainly caused by EGFR T790M secondary mutation. In the current study, we investigated whether the root extract of Scutellaria baicalensis (SB) overcomes gefitinib resistance. Gefitinib-resistant H1975 human NSCLC cells (EGFR L858R/T790M double mutant) were treated with gefitinib and/or ethanol extract of SB (ESB) to evaluate the effect of ESB on the gefitinib sensitivity. The cell viability was measured by MTT assay and trypan blue exclusion assay. The colony-forming ability was evaluated by anchorage-dependent colony formation assay. Combined treatment with gefitinib and ESB markedly decreased the cell viability and colony formation than single treatment with gefitinib or ESB in H1975 cells. In addition, cells treated with both gefitinib and ESB exhibited a significant increase of sub-G1 DNA content which indicates apoptotic cells compared with those treated with gefitinib or ESB alone. As a molecular mechanism, combined treatment with gefitinib and ESB strongly downregulated the phosphorylation of ERK and JNK than single treatment with gefitinib or ESB. Taken together, our results demonstrate that ESB sensitizes H1975 cells to gefitinib treatment. We cautiously propose that ESB can be used in combination with gefitinib for the advanced NSCLC patients with acquired resistance to EGFR TKIs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.84 no.2
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• pp.89-95
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• 2021

Lung cancer is one of the leading causes of cancer-related deaths in Korea. Although the smoking rate has decreased over time, the prevalence of lung cancer still remains high. In this study, we reviewed recent trends on the incidence, epidemiology, screening, diagnosis, and treatment of lung cancer in Korea by analyzing data from the national lung cancer registry and recently-published studies. Although approximately 40% of patients with non-small cell lung cancer (NSCLC) were diagnosed as stage IV, the 5-year relative survival rate improved from 11.3% (1993-1995) to 30.2% (2013-2017), possibly due to advances in methods of diagnosis and therapy. In addition, the 2019 implementation of the national lung cancer screening program with low-dose computed tomography may have also contributed to these improvements in survival rates. Recently, molecular diagnosis has become more widely used in the identification of genetic mutations in tissue specimens. Target therapy and immune checkpoint inhibitors have also been successfully used, particularly in cases of advanced NSCLC. In the future, further research on the optimal management of lung cancer remains necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2987-2991
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• 2015

Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (${\leq}60$ vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Conclusions: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.689-692
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• 2015

Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. Materials and Methods: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. Results: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. Conclusions: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2685-2688
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• 2014

Background: To explore the prevalence of lymphocyte subgroups $CD3^+$ $CD4^+$ and $CD3^+$ $CD8^+$ and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer (NSCLC). Materials and Methods: A total of 40 patients with NSCLC were divided into different groups according to different clinical factors (TNM staging, pathological patterns and genders) for assessment of relations with $CD3^+$ $CD4^+$ and $CD3^+$ $CD8^+$ and the surface receptors NKG2D and NKG2A of T lymphocytes in peripheral blood by flow cytometry. Results: Patients in the advanced group had evidently lower levels of $CD3^+$ $CD4^+$ but markedly higher levels of $CD3^+$ $CD8^+$ in peripheral blood than those with early lesions (p<0.05). In addition, NSCLC patients in the advanced group had obviously higher $CD3^+$ $CD4^+$ NKG2D and $CD3^+$ $CD8^+$ NKG2A expression rates but lower $CD3^+$ $CD4^+$ NKG2A and $CD3^+$ $CD8^+$ NKG2D expression rates (p<0.05). However, there were no significant differences between NSCLC patients with different genders and pathological patterns in expression levels of lymphocyte subgroups $CD3^+$ $CD4^+$ and $CD3^+$ $CD8^+$ and their surface receptors NKG2D and NKG2A. Conclusions: Unbalanced expression of surface receptors NKG2D and NKG2A in $CD3^+$ $CD4^+$ and $CD3^+$ $CD8^+$ lymphocytes may be associated with a poor prognosis, greater malignancy and immunological evasion by advanced cancers, related to progression of lung cancer.