• Journal of Chest Surgery
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• v.57 no.5
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• pp.460-466
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• 2024

Background: Numerous studies have investigated methods of predicting postoperative pulmonary complications (PPCs) in lung cancer surgery, with chronic obstructive pulmonary disease (COPD) and low forced expiratory volume in 1 second (FEV₁) being recognized as risk factors. However, predicting complications in COPD patients with preserved FEV₁ poses challenges. This study considered various diffusing capacity of the lung for carbon monoxide (DL_CO) parameters as predictors of pulmonary complication risks in mild COPD patients undergoing lung resection. Methods: From January 2011 to December 2019, 2,798 patients undergoing segmentectomy or lobectomy for non-small cell lung cancer (NSCLC) were evaluated. Focusing on 709 mild COPD patients, excluding no COPD and moderate/severe cases, 3 models incorporating DL_CO, predicted postoperative DL_CO (ppoDL_CO), and DL_CO divided by the alveolar volume (DL_CO/VA) were created for logistic regression. The Akaike information criterion and Bayes information criterion were analyzed to assess model fit, with lower values considered more consistent with actual data. Results: Significantly higher proportions of men, current smokers, and patients who underwent an open approach were observed in the PPC group. In multivariable regression, male sex, an open approach, DL_CO <80%, ppoDL_CO <60%, and DL_CO/VA <80% significantly influenced PPC occurrence. The model using DL_CO/VA had the best fit. Conclusion: Different DL_CO parameters can predict PPCs in mild COPD patients after lung resection for NSCLC. The assessment of these factors using a multivariable logistic regression model suggested DL_CO/VA as the most valuable predictor.

• Radiation Oncology Journal
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• v.35 no.2
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• pp.153-162
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• 2017

Purpose: To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Materials and Methods: Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ${\pm}$ boost (WBRT ${\pm}$ boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). Results: The WBRT ${\pm}$ boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ${\pm}$ boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ${\geq}42.3Gy$ compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Conclusions: Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.359-366
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• 2005

Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

• Journal of Yeungnam Medical Science
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• v.21 no.2
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• pp.198-206
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• 2004

Background: To evaluate the efficacy and safety of paclitaxel and cisplatin against advanced non-small cell lung cancer (NSCLC) as a second-line chemotherapy. Subjects and Methods: Twenty-five patients were enrolled. The patients received 200 $mg/m^2$ paclitaxel as a 3-hour intravenous infusion and 60 $mg/m^2$ cisplatin as 2D-minute intravenous infusion with vigorous hydration on day 1 every 28 days. The response was assessed every 2 cycles. Results: All 25 patients were assessed for their response and toxicity. Partial responses were observed in 5 patients. The overall response rate was 20%(95% confidence interval, 4%-36%) and the median response duration was 4.5(range, 2-11) months. The median time to progression was 3.3(range, 0-14) months. The median overall survival of all patients was 7.4(range, 1.3-39) months. The hematologic toxicities were minor and easily controlled. Conclusion: The combination chemotherapy of paclitaxel and cisplatin as a second-line treatment has a moderate efficacy with an acceptable toxicity in patients with advanced NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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• pp.15-23
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• 2012

Background: The survival of non-small cell lung cancer (NSCLC) patients with brain metastases is reported to be 3~6 months even with aggressive treatment. Some patients have very short survival after aggressive treatment and reliable prognostic scoring systems for patients with cancer have a strong correlation with outcome, often supporting decision making and treatment recommendations. Methods: A total of one hundred twenty two NSCLC patients with brain metastases who received gamma knife radiosurgery (GKRS) were analyzed. Survival analysis was calculated in all patients for thirteen available prognostic factors and four prognostic scoring systems: score index for radiosurgery (SIR), recursive partitioning analysis (RPA), graded prognostic assessment (GPA), and basic score for brain metastases (BSBM). Results: Age, Karnofsky performance status, largest brain lesion volume, systemic chemotherapy, primary tumor control, and medication of epidermal growth factor receptor tyrosine kinase inhibitor were statistically independent prognostic factors for survival. A multivariate model of SIR and RPA identified significant differences between each group of scores. We found that three-tiered indices such as SIR and RPA are more useful than four-tiered scoring systems (GPA and BSBM). Conclusion: There is little value of RPA class III (most unfavorable group) for the same results of 6-month and 1-year survival rate. Thus, SIR is the most useful index to sort out patients with poorer prognosis. Further prospective trials should be performed to develop a new molecular- and gene-based prognostic index model.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.77-81
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• 2015

Background: The aim of the study was to determine whether the expression of baseline phosphorus (P) and magnesium (Mg) levels were prognostic in terms of stage and overall survival (OS) in newly diagnosed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Materials and Methods: Retrospectively, 130 patients were selected at the time of diagnosis oflung cancer (100 with NSCLC and 30 with SCLC), before the initialization of any chemo-radiotherapy. The median age was 67 (range 29-92). IA, IB, IIA, IIB, IIIA, IIIB and IV stages were present in 3, 4, 19, 6, 25, 8, and 65 patients, respectively. After centrifugation, the levels of serum P and Mg were measured using the nephelometric method/ photometry and evaluated before any type of treatment. Results: Higher than normal levels of P were found in 127/130 patients, while only four patients had elevated Mg serum values. In terms of Spearman test, higher P serum values correlated with either stage (rho=- 0.334, p<0.001) or OS (rho=-0.212, p=0.016). Additionally, a significant negative correlation of Mg serum levels was found with stage of disease (rho=-0.135, P=0.042). On multivariate cox-regression survival analysis, only stage (p<0.01), performance status (p<0.01) and P serum (p=0.045) showed a significant prognostic value. Conclusions: Our study indicated that pre-treatment P serum levels in lung cancer patients are higher than the normal range. Moreover, P and Mg serum levels are predictive of stage of disease. Along with stage and performance status, the P serum levels had also a significant impact on survival. This information may be important for stratifying patients to specific treatment protocols or intensifying their therapies. However, larger series are now needed to confirm our results.

• The Journal of the Society of Stroke on Korean Medicine
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• v.23 no.1
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• pp.1-12
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• 2022

Persistent hiccups persist for more than 48 hours. Those can often occur in cancer patients after chemotherapy or high dose of corticosteroids. A 52-year-old male patient undergoing Non-small cell lung cancer(NSCLC), recently suffered presistent hiccups and dyspnea. He was treated with herbal medicine for 56days and acupuncture for 9days. No side effects were observed during treatment. The severity of hiccups was measured in every hospital visit and psychometric symptoms were evaluated periodically through the Edmonton Symptom Assessment System(ESAS). The severity of hiccups and psychometric symptoms were alleviated and the effect persisted during the treatment. The patient took no other nervous system drugs in the end of the treatment. In conclusion, Korean medicine like Hyeongbangjihwang-tang and Jeongcheonhwadamgangki-tang can be effective for patients with persistent hiccups and dyspnea who cannot use alternative drugs or treatment because of other complications.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.271-278
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• 2010

Background: Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability. Methods: A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis. Results: The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group. Conclusion: EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.

• Tuberculosis and Respiratory Diseases
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• v.73 no.6
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• pp.303-311
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• 2012

Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.