• Journal of Chest Surgery
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• v.53 no.1
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• pp.22-27
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• 2020

Background: Previous studies have shown that lung cancer stem cells express CD133 and that certain cancer stem cells express cancer germline antigens (CGAs). The transcriptional regulation of CD133 is complicated and poorly understood. We investigated CD133 and CGA expression in a non-small cell lung cancer cell line. Methods: The expression levels of CD133 and CGAs (MAGE-6, GAGE, SSX, and TRAG-3) were measured in an NCI-H292 lung cancer cell line. The methylation status of the CD133 gene promoter region was analyzed. The expression levels and promoter methylation statuses of CD133 and CGAs were confirmed by treatment with the demethylating agent 5-aza-2'-deoxycytidine (ADC). Results: After treatment with ADC, CD133 expression was no longer detected. MAGE-6 and TRAG-3 were detected before ADC treatment, while GAGE and SSX were not detected. ADC treatment upregulated MAGE-6 and TRAG-3 expression, while GAGE expression was still undetected after treatment, and only weak SSX expression was observed. GAGE expression was not correlated with expression of CD133, while the levels of expression of MAGE-6, TRAG-3, and SSX were inversely correlated with CD133 expression. Conclusion: These results showed that CD133 expression can be regulated by methylation. Thus, the demethylation of the CD133 promoter may compromise the treatment of lung cancer by inactivating cancer stem cells and/or activating CGAs.

• Korean Journal of Bronchoesophagology
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• v.17 no.1
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• pp.5-8
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• 2011

The proliferation of new technologies has significantly enhanced the diagnostic capabilities of flexible bronchoscopy compared with traditional methods. Narrow band imaging (NBI), an optical technique in which filtered light enhances superficial neoplasms based on their neoangiogenic patterns, was developed to screen for central intraepithelial moderate or severe dysplasia, carcinoma in situ (CIS), and microinvasive neoplasia in patients at risk for lung cancer. Because angiogenesis occurs preferentially in dysplastic and neoplastic lesions, NBI may identify early dysplastic lesions better than white light bronchoscopy (WLB) currently in use. NBI bronchoscopy can be used not only to detect precancerous lesions, but also to screen for cancerous lesions. We prospectively evaluated 101 patients with suspected lung cancer between July 2009 and June 2010. All were previously scheduled for flexible bronchoscopy CT scans. Abnormal NBI was defined by Shibuya's descriptors (tortuous, dotted, or spiral and screw patterns). Biopsies of 132 lesions in 92 patients showed that 78 lesions (59.1%) were malignant and 54 (40.9%) were benign. The diagnostic sensitivity of bronchoscopy in detecting malignancy was 96.2% (75/78). When assorted by lesion pattern, the sensitivity and specificity of NBI bronchoscopy in detecting malignancies were 69.2% (54/78) and 96.3% (52/54), respectively, for the spiral and screw pattern and 14.1% (11/78) and 96.3% (52/54), respectively, for the dotted pattern. Unexpectedly, additional cancerous lesions were detected in five patients (2 dotted and 3 spiral and screw). As a screening tool for malignant lesions, NBI bronchoscopy should assess combinations of all three lesion. The dotted and spiral and screw patterns may be helpful in determining which lesions should be biopsied. NBI bronchoscopy may be useful not only for the diagnosis of early-stage lung cancer but also for more accurate local staging of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.214-217
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• 2013

Treatment of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is difficult because the mortality rate after surgery or chemotherapy is high for these patients. Spontaneous regression of cancer is rare, especially in lung cancer. A 62-year-old man, previously diagnosed with IPF, presented with stage IIIC (T2N3M0) non-small cell lung cancer. About 4 months later, spontaneous regression of the primary tumor was observed without treatment. To the best of our knowledge, this is the first report of spontaneous regression of lung cancer in a patient with IPF.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.211-216
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• 2019

Background: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel $25mg/m^2$ on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.217-226
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• 2019

Background: Depression is a recognized complication of lung cancer underreported in developing countries such as Malaysia. Treating and identifying depression in cancer patients increases survival and quality of life. Our objectives are to study prevalence of depressive symptoms in newly diagnosed lung carcinoma, and examine the relationship of depressive symptoms with other influencing risk factors. Methods: A 2-year, cross sectional study February 2015-February 2017, was conducted at Hospital Tengku Ampuan Afzan, and Penang General Hospital. One hundred and three patients with newly diagnosed, biopsy confirmed primary lung carcinoma were recruited. Self-rated patient's identification sheet, validated Center for Epidemiologic Studies Depression (CES-D), and Dukes University Religion Index score from three different main languages were used. Results: Prevalence of current depressive symptoms (CES-D total score ${\geq}16$) is 37.9%. The result suggests prevalence of those at high risk of moderate to major depression, may need treatment. Multivariate analysis reveals those with good Eastern Cooperation Oncology Group factor (${\eta}2=0.24$, p<0.001) married (${\eta}2=0.14$, p<0.001) with intrinsic religiosity (IR) (${\eta}2=0.07$, p<0.02) are more resistant to depression. Conclusion: One in three of lung carcinoma patients, are at increased risk for depression. Clinicians should be aware that risk is highest in those with poor performance status, single, and with poor IR. We suggest routine screening of depression symptoms as it is feasible, to be performed during a regular clinic visit with immediate referral to psychiatrist when indicated.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.62-70
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• 2019

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. Methods: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were independent predictors of PFS. ECOG PS 0-1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.20-29
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• 2022

Background: Patients with high-risk (HR) operable non-small cell lung cancer (NSCLC) may have unique prognostic factors. This study aimed to evaluate surgical outcomes in HR patients and to investigate prognostic factors in HR patients versus standard-risk (SR) patients. Methods: In total, 471 consecutive patients who underwent curative lung resection for NSCLC between January 2012 and December 2017 were identified and reviewed retrospectively. Patients were classified into HR (n=77) and SR (n=394) groups according to the American College of Surgeons Oncology Group criteria (Z4099 trial). Postoperative complications were defined as those of grade 2 or higher by the Clavien-Dindo classification. Results: The HR group comprised more men and older patients, had poorer lung function, and had more comorbidities than the SR group. The patients in the HR group also experienced more postoperative complications (p≤0.001). More HR patients died without disease recurrence. The postoperative complication rate was the only significant prognostic factor in multivariable Cox regression analysis for HR patients but not SR patients. HR patients without postoperative complications had a survival rate similar to that of SR patients. Conclusion: The overall postoperative survival of HR patients with NSCLC was more strongly affected by postoperative complications than by any other prognostic factor. Care should be taken to minimize postoperative complications, especially in HR patients.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.30-36
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• 2022

Background: No consensus exists regarding whether volatile anesthetics are superior to intravenous anesthetics for reducing postoperative pulmonary complications (PPCs) in patients undergoing general anesthesia for surgery. Studies of this issue focused on anatomic pulmonary resection are lacking. This study compared the effects of total intravenous anesthesia (TIVA) versus volatile anesthesia on PPCs after anatomic pulmonary resection in patients with lung cancer. Methods: This retrospective study examined the medical records of patients with lung cancer who underwent lung resection at our center between January 2018 and October 2020. The primary outcome was the incidence of PPCs, which included prolonged air leak, pneumonia, acute respiratory distress syndrome, empyema, atelectasis requiring bronchofiberscopy (BFS), acute lung injury (ALI), bronchopleural fistula (BPF), pulmonary embolism, and pulmonary edema. Propensity score matching (PSM) was used to balance the 2 groups. In total, 579 anatomic pulmonary resection cases were included in the final analysis. Results: The analysis showed no statistically significant difference between the volatile anesthesia and TIVA groups in terms of PPCs, except for prolonged air leak. Neither of the groups showed atelectasis requiring BFS, ALI, BPF, pulmonary embolism, or pulmonary edema after PSM. However, the length of hospitalization, intensive care unit stay, and duration of chest tube indwelling were shorter in the TIVA group. Conclusion: Volatile anesthetics showed no superiority compared to TIVA in terms of PPCs after anatomical pulmonary resection in patients with lung cancer. Considering the advantages of each anesthetic modality, appropriate anesthetic modalities should be used in patients with different risk factors and situations.

• Journal of Nutrition and Health
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• v.56 no.1
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• pp.12-23
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• 2023

Purpose: This study investigates the alterations in A549 human non-small-cell lung cancer (NSCLC) cells exposed to Citrus junos extract (CJE). We further examine the antiproliferative and apoptotic effects of CJE on NSCLC cells. Methods: Inhibition of proliferation was examined by applying the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) colorimetric assay on CJE-treated A549 NSCLC cells. The lactate dehydrogenase (LDH) assay was performed to measure the degree of toxicity of CJE on NSCLC cells. The effect on migratory proliferation was confirmed using the scratch wound healing assay. The antiproliferative effect of the CJE on human lung cancer cells was verified through morphological observation, fluorescence microscopy, and caspase-3 colorimetry. Results: Exposure of NSCLC cells to CJE resulted in a dose- and time-dependent decrease in cell activity and increased toxicity to the cells. In addition, microscopic observation revealed a reduced ability of the cancer cells to migrate and proliferate after exposure to the CJE, with simultaneous morphological apoptotic changes. Fluorescence staining and microscopic examination revealed that this death was a process of self-programmed cell death of NSCLC cells. Compared to unexposed NSCLC cells, the expression of caspase-3 was significantly increased in cells exposed to CJE. Conclusion: Exposure of A549 human NSCLC cells to CJE inhibits the proliferation, increases the cytotoxicity, and decreases the ability of cells to migrate and grow. Moreover, the expression of caspase-3 increases after CJE treatment, suggesting that the apoptosis of NSCLC cells is induced by a chain reaction initiated by caspase-3. These results indicate that Citrus junos is a potential therapeutic agent for human non-small-cell lung cancer.

• Investigative Magnetic Resonance Imaging
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• v.26 no.1
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• pp.32-42
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• 2022

Purpose: To evaluate the clinical benefit of 2D contrast-enhanced T2 fluid-attenuated inversion recovery (CE-T2 FLAIR) image for detecting leptomeningeal metastasis (LM) in the brain metastasis work-up for lung cancer. Materials and Methods: From June 2017 to July 2019, we collected all consecutive patients with lung cancer who underwent brain magnetic resonance image (MRI), including contrast-enhanced 3D fast spin echo T1 black-blood image (CE-T1WI) and CE-T2 FLAIR; we recruited clinico-radiologically suspected LM cases. Two independent readers analyzed the images for LM in three sessions: CE-T1WI, CE-T2 FLAIR, and their combination. Results: We recruited 526 patients with suspected lung cancer who underwent brain MRI; of these, we excluded 77 (insufficient image protocol, unclear pathology, different contrast media, poor image quality). Of the 449 patients, 34 were clinico-radiologically suspected to have LM; among them, 23 were diagnosed with true LM. The calculated detection performance of CE-T1WI, CE-T2 FLAIR, and combined analysis obtained from the 34 suspected LM were highest in the combined analysis (AUC: 0.80, 0.82, and 0.89, respectively). The inter-observer agreement was also the highest in the combined analysis (0.68, 0.72, and 0.86, respectively). In quantitative analyses, CNR of CE-T2 FLAIR was significantly higher than that of CE-T1WI (Wilcoxon signed rank test, P < 0.05). Conclusion: Adding CE-T2 FLAIR might provide better detection for LM in the brain-metastasis screening for lung cancer.