• Journal of Pharmacopuncture
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• v.21 no.4
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• pp.268-276
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• 2018

Objectives: The purpose of this study is to investigate the anti-cancer effects of different fractions of Astragalus membranaceus (AM) in human non-small cell lung cancer (NSCLC) cells. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AM. The cell death was examined by MTT assay and trypan blue exclusion assay. Apoptosis was detected by DAPI staining, annexin V-PI double staining and cell cycle analysis. The expression of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) was examined by western blot. Results: Among various fractions of AM, the ethyl acetate fraction of AM (EAM) showed the strongest cytotoxic effect in NSCLC cells. EAM reduced the cell proliferation in a time- and dose-dependent manner in NSCLC cells. In addition, EAM induced the chromatin condensation, and increased the population of sub-G1 phase and annexin V-positive cells in a time-dependent manner, indicating that EAM induced apoptosis in NSCLC cells. Consistently, EAM enhanced the expression of cleaved caspase-8 and -9, and induced the accumulation of cleaved- poly (ADP-ribose) polymerase (PARP). Among MAPK proteins, only ERK was dephosphorylated by EAM, suggesting that ERK might be related with EAM-induced apoptosis. Conclusion: Our results clearly demonstrate that EAM exhibited anti-cancer effects in NSCLC cells by induction of apoptosis. We provide a valuable evidence which suggests that AM could be a desirable therapeutic option for treatment of NSCLC.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.171-176
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• 2018

Background: Small cell lung cancer (SCLC) tends to grow more rapidly and spread much faster than non-small cell lung cancer (NSCLC). A concurrent combination of chemotherapy and thoracic radiotherapy is suggested as the standard conventional treatment, but it is more challenging for elderly patients having pulmonary and cardiovascular comorbidities. Case presentation: Here we present a case of an 80-year-old male, current smoker diagnosed with SCLC in limited stage T3N0M0 (36mm right upper lobe, satellite nodule) in Dec, 2015. The standard concurrent chemoradiotherapy was not available for his comorbidities, which included chronic obstructive pulmonary disease (COPD) and angina pectoris. Furthermore, he and his family refused the recommended chemotherapy or radiotherapy exclusively. Alternatively, he received various non-conventional treatments including local radiofrequency hyperthermia, mistletoe, and Traditional Korean medicine including acupuncture, moxibustion and herbs since Jan. 2016. Despite the progression in primary tumor size, there have been no other distant relapse so far, and the patient has been in stable condition ever since. Conclusion: We suggest that a combination of various alternative treatments could be a candidate for elderly patients intolerable to conventional cytotoxic treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1557-1561
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• 2012

Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods: Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. Conclusion: These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.630-641
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• 2008

Gamisamgibopae-tang (GMSGBPT) is a traditional Korean medicine, which has been used for patients suffering from a lung disease in Oriental medicine. In the present study, we examined the biochemical mechanisms of apoptosis by GMSGBPT in NCI-H460 and A549 human non-small-cell lung cancer cell lines. It was found that GMSGBPT could inhibit the cell proliferation of A549 cells in a concentration-dependent manner, however GMSGBPT did not affect the cell proliferation of NCI-H460 cells. Apoptotic cell death in A549 cells were detected using DAPI staining and annexin V fluorescein methods. The induction of apoptotic cell death by GMSGBPT was connected with a down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression, and proteolytic activation of caspase-3 and caspase-9 in A549 cells. However, GMSGBPT did not affect the levels of pro-apoptotic Bax and Bad expression, and activity of caspase-8. GMSGBPT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, phospholipase C-1 (PLC${\gamma}$1) and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings suggest that GMSGBPT may be a potential chemotherapeutic agent for the control of human non-small-cell lung cancer cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of GMSGBPT.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.352-358
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• 2005

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC). The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining. None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05). In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4693-4697
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• 2016

Aim: The objective of this study is to investigate prognostic factors affecting survival of patients undergoing concurrent or sequential chemoradiotherapy (CRT) for stage III non-small-cell lung cancer (NSCL). Methods and materials: We retrospectively reviewed the clinical records of 148 patients with advanced, inoperable stage III NSCLC, who were treated between 2007 and 2015. Results: The median survival was found to be 19 months and 3-year overall survival was 27%. Age (<65 vs ${\geq}65years$, p=0.026), stage (IIIA vs IIIB, p=0.033), dose of radiotherapy (RT) (<60 vs ${\geq}60Gy$, p=0.024) and treatment method (sequential chemotherapy+RT vs concurrent CRT, p=0.023) were found to be factors affecting survival in univariate analyses. Gender, histological subtype, weight loss during CRT, performance status, induction/consolidation chemotherapy and presence of comorbidities did not affect survival (p>0.050). Conclusion: Young age, stage IIIA, radiotherapy dose and concurrent chemoradiotherapy may positively affect survival in stage III NSCL cases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1421-1425
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• 2015

Aims: Pleiotrophin (PTN), an angiogenic factor, is associated with various types of cancer, including lung cancer. Our aim was to investigate the possibility of using serum PTN as an early indicator regarding disease diagnosis, classification and prognosis, for patients with non-small cell lung cancer (NSCLC). Methods: Significant differences among PTN levels in patients with small cell lung cancer (SCLC, n=40), NSCLC (n=136), and control subjects with benign pulmonary lesions (n=21), as well as patients with different pathological subtypes of NSCLC were observed. Results: A serum level of PTN of 300.1 ng/ml, was determined as the cutoff value differentiating lung cancer patients and controls, with a sensitivity and specificity of 78.4% and 66.7%, respectively. Negative correlations between serum PTN level and pathological differentiation level, stage, and survival time were observed in our cohort of patients with NSCLC. In addition, specific elevation of PTN levels in pulmonary tissue in and around NSCLC lesions in comparison to normal pulmonary tissue obtained from the same subjects was also observed (n=2). Conclusion: This study suggests that the serum PTN level of patients with NSCLC could be an early indicator for diagnosis and prognosis. This conclusion should be further assessed in randomized clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2563-2566
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• 2013

Background: Interleukin-33 (IL-33) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of serum IL-33 in patients with non-small-cell lung cancer (NSCLC). Methods: Sera collected from 250 healthy volunteers (HV), 256 patients with benign lung diseases (BLD) and 262 NSCLC cases were subjected to IL-33 ELISA and relationships between serum IL-33 and clinical characteristics were evaluated. Results: Circulating IL-33 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). Using a cut-off level 68 pg/ml (95% specificity in the HV group), IL-33 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that serum IL-33 was an independent prognostic factor in the entire NSCLC group [hazards ratio (HR) = 0.64 for low versus high IL-33 levels, 95% confidence interval (CI) 0.50-0.82; p<0.001] and in 165 selected patients with locally advanced or metastatic disease receiving chemoradiotherapy or chemotherapy (HR 0.70, 95% CI 0.52-0.94; p=0.013). Conclusions: IL-33 is a promising potential diagnostic and prognostic marker in NSCLC, independent of the therapeutic intervention.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.16-24
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• 2017

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.505-513
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• 2004

Background : In lung cancer patients, the presence of metastatic neck nodes is a crucial indicator of inoperabilty. So thorough physical examination of neck is always mandatory, but sometimes those are hardly palpable even by the skillful hand. Ultrasonography is a useful diagnostic method in detection of small impalpable lymph nodes and in guidance of fine needle aspiration biopsy. In this study we evaluated the clinical usefulness of ultrasonography(USG) and ultrasound-guided fine needle aspiration cytology(US-FNA) in lung cancer patients without palpable neck nodes. Methods and Materials : From Sep 2002 to Sep 2003, 36 non-small cell lung cancer patients (20 adenocarcinoma, 16 squamous cell cancer) and 10 small cell lung cancer patients without palpable neck nodes on physical examiation were enrolled. patients who had contralateral mediastinal nodal enlargement(>1cm) on chest CT were excluded. After the routine check of USG on the neck, US-FNA was done in cases with enlarged neck nodes (${\geq}5mm$ in the short axis). The presence of enlarged lymph node on USG, and of malignant cells on cytology were evaluated by the histological type and the patients' clinical stage of lung cancer. Results : Among 36 non-small lung cell cancer patients, 14 (38.8%) had enlarged neck nodes on USG, and 5 of 10 small cell lung carcinoma patients. The mean diameter of the neck nodes was 9.8 mm (range, 7-12 mm). US-FNA of 14 non-small cell lung cancer patients revealed tumor cells in eight patients (57.1%). In 5 small cell lung cancer pateints, tumor cells were found in all cases. By the result of US-FNA, the clinical stage of 8 out of 36 (22.2%) non-small cell lung cancer patients had changed, including two cases of shift from the operable IIIa to the inoperable IIIb. In small cell lung cancer patients their clinical stage was not changed after US-FNA, but their pathological diagnosis was easily done in two cases, in whom endobronchial lesions were not found on bronchoscopy. Conclusions : USG and US-FNA of neck node seem to be safe, sensitive and cost-effective diagnostic tools in the evaluation of lung cancer patients without palpable neck nodes.