• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5473-5476
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• 2013

Background: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. Materials and Methods: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. Results: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). Conclusions: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.11-21
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• 2012

Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of $p16^{INK4A}$ immunoexpression. Results: Hypermethylation of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with $p16^{INK4A}$ immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of $p16^{INK4A}$ immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed $p16^{INK4A}$ immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and $p16^{INK4A}$ immunoexpression loss.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.413-422
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• 2020

Delphinidin is a major anthocyanidin compound found in various vegetables and fruits. It has anti-oxidant, anti-inflammatory, and various other biological activities. In this study we demonstrated the anti-cancer activity of delphinidin, which was related to autophagy, in radiation-exposed non-small cell lung cancer (NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxic dose of delphinidin (5 μM) before exposure to γ-ionising radiation (IR). We found that treatment with delphinidin or IR induced NSCLC cell death in vitro; however the combination of delphinidin pre-treatment and IR was more effective than either agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethal dose. Moreover, combined treatment with delphinidin and IR, enhanced apoptotic cell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway. Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increased the expression of autophagy-induced cell death associated-protein in radiation-exposed NSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidin pre-treatment in radiation-exposed NSCLC cells. Collectively, these results show that delphinidin acts as a radiation-sensitizing agent through autophagy induction and JNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

• Journal of Korean Traditional Oncology
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• v.23 no.2
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• pp.11-25
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• 2018

Objective: The purpose of this study is to report the case of a patient with non-small cell lung cancer (NSCLC) with Programmed cell death protein 1 (PD-1) mutation treated by Integrative Medicine Therapy (IMT). Methods: A patient with metastatic NSCLC received pembrolizumab 200mg intravenously for every 3 weeks from July 2017. Repeat cycle every 3 weeks since July 2017. The patient has been treated with Integrative Medicine Therapy (IMT) since December 2016. The tumor size was measured by computed tomography (CT) and magnetic resonance imaging(MRI). Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Results: After combined treatment, the extent of proximal portion of primary tumor in the left lower lobe was decreased and disease status was stable radiologically. No evidence of newly developed metastatic lesions in the brain since May 2017. The patient did not experience any adverse event according to NCI-CTCAE ver. 5.0. Conclusion: This case study suggests that Integrative Medicine Therapy (IMT) may contribute to tumor response, in conjunction with Pembrolizumab on the treatment of patients with NSCLC.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.200-209
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• 2023

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.229-234
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• 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Indigo Naturalis (IN) is a dark blue powder obtained by processing leaves or stems of indigo plants, its anticancer effects have been reported in several studies. However, the pharmacological mechanism of IN in small cell lung cancer (SCLC) is not elucidated. In this study, to investigate the anticancer efficacy of IN for SCLC, we presented potential active ingredients, SCLC-related targets, and pharmacological mechanisms of IN that are expected to have anticancer activity for SCLC using a network pharmacological analysis. The phytochemical compounds of IN have been collected through TCMSP, SymMap, or HPLC documents. The active ingredients of IN such as indirubin, indican, isatin, and tryptanthrin were selected through ADME parameters or literature investigations for each compound. Using the Compounds, Disease-Target associations Databases, 124 common targets of IN and SCLC were obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis was carried out. GO biological processes are associated with response to xenobiotic stimulus, positive regulation of protein phosphorylation, regulation of mitotic cell cycle, and regulation of apoptotic signaling pathway. KEGG disease pathways included Gastric cancer, Bladder cancer, SCLC, and Melanoma. The main anticancer targets of the IN for SCLC were analyzed in 14 targets, including BCL2, MYC, and TP53. In conclusion, the results of this study based on the network pharmacology of IN can provide important data for the effective prevention and treatment of SCLC.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• Journal of Animal Science and Technology
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• v.45 no.4
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• pp.593-606
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• 2003

This study was conducted to develop effective manufacturing methods of a total mixed ration(TMR) composed of broiler litter(BL) and bakery by-product(BB) for ruminants. Five experiments included a small-scaled manufacture of TMR using a deepstacking method(Exp. 1), its pelletization(Exp. 2), its field-scaled manufacture(Exp. 3), a field-scaled manufacture using an ensiling method(Exp. 4), and a mixing process of deepstacked BL and BB prior to feeding(Exp. 5). BL and BB were mixed at a ratio which makes total digestible nutrients of the TMR 69%. For each experiment, temperature, appearance and physico-chemical properties were recorded and analyzed. The chemical composition data revealed that the mixture of BL and BB showed nutritionally additive balance which resulted from a considerable increase(P<0.05) of organic matter and a desirable decrease(P<0.05) of protein and fiber up to the requirement level for growing ‘Hanwoo’ steers. Deepstacking of BL and BB in Exp. 1 and 3 resulted in a sufficient increase of stack temperature for pasteurization, little chemical losses, appearance of white fungi on the surface, and partial charring due to excess stack temperature. For Exp. 2, its pelleting, which was successful using a simple, small-scaled pelletizer, resulted in a little loss(P<0.05) of organic matter and an increase(P<0.05) of indigestible protein(ADF-CP). Ensiling the mixture in Exp. 4 made little effect on chemical composition; however, one month of the ensiling period was not enough for favorable silage parameters. Deepstacking BL alone in Exp. 5 tended(P<0.1) to decrease true protein : NPN ratio and hemicellulose content and increase ADF-CP content due to the heat damage occurred. Deepstacking or ensiling of BL-BB mixtures and simple incorporating of BB into deepstacked BL prior to feeding could be practical and nutrients-preservative methods in TMR manufacture for beef cattle, although ensiling needed further hygienic evaluation.

• Korean Journal of Food Science and Technology
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• v.21 no.2
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• pp.192-196
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• 1989

This experiment was carried out to compare the difference of lipid components, amino acid composition by size of sea eel. Large sea eel(length 57.5-60.0cm, weight 269.5-300.0g) was higher in moisture and crude protein content, and lower in crude lipid content than those of small sea eel(28.8-31.2cm, 39.5-43.6g). Total lipid(TL) of large and small sea eel were consisted of 89.7%, 93.3% neutral lipid, 8.9%, 5.2% phospholipid, and 1.4%, 1.5% glycolipid, respectively. In fatty acid composition of TL, large fishes revealed higher content in polyunsaturated fatty acids such as 20:5, 22:5, 22:6, while lower in saturates and monoenes such as 16:0, 16:1, 18:1 than those of small fishes. The major fatty acids of these fishes were generally 18:1, 16:0, 22:6, 16:1 and 20:5 in order. Total amino acid contents of large and small sea eel were 17022.7mg/100g, 15409.4mg/100g. And the main amino acids were aspartic acid, glutamic acid, isoleucine, leucine, lysine, arginine. Large fishes was higher in cystine, methionine, tyrosine, phenylalanine content, while lower in aspartic acid, glutamic acid than those of small ones.

• Culinary science and hospitality research
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• v.19 no.5
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• pp.158-169
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• 2013

Finespotted flounder, used for a representative raw fish in spring, is considered comparatively difficult to breed, which causes small Olive flounder and Stone flounder from China, similar kinds of flounders, to appear on the market for sale under the name of 'Finespotted flounder.' The reason lies under the considerations that small Olive flounder and Stone flounder from China are relatively lower priced and in higher supply and demand, being difficult to distinguish from Finespotted flounder when sliced with bones. Thus, the purpose of our thesis is to distinguish Finespotted flounder from similar kinds of fish analyzing the lipid content in slices of raw fish and SDS-PAGE(sodiumdodecylsullipide-polyacrylamide gel eletrophoresis). Upon comparing the main components between sliced Finespotted flounder and similar kinds of fish, such as small Olive flounder and Stone flounder from China, we found that there are no noticeable differences among them in moisture content, and little, if any noticeable differences, in crude protein and ash content(P>0.05). Based on these analyses, we have conclude that commercial raw fish restaurants sell small Olive flounder and Stone flounder under the name of Finespotted flounder. However, a variety of factors have an effect on our analysis, such as the individual characteristics of fish and a seasonal variation. The aim of our analysis is to enhance more accurate distinction criteria, although some fish kinds can be discerned with our present technique of examining lipid content and SDS-PAGE. Through more sophisticated analyses developed by consistent research, we look forward to attaining more accurate techniques for discerning between Finespotted flounder and different kinds of similar fish.