• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.986-992
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• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

• Journal of Life Science
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• v.28 no.1
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• pp.37-42
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• 2018

Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.

• Journal of Life Science
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• v.28 no.1
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• pp.116-129
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• 2018

Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.1-7
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• 2009

Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3997-4002
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• 2015

Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6463-6468
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• 2015

Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6191-6196
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• 2012

Aims and Background: Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside $Rg_1$ ($Rg_1$), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether $Rg_1$ can induce cancer cell senescence is still unclear. Methods: In the current study, human leukemia K562 cells were subjected to $Rg_1$ exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of $Rg_1$ on cell cycle were analyzed using flow cytometry and by SA-${\beta}$-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. Results: K562 cells demonstrated a maximum proliferation inhibition rate with an $Rg_1$ concentration of $20{\mu}\;mol{\cdot}L^{-1}$ for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-${\beta}$-galactosidase (SA-${\beta}$-Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin $G_2$/M phase after $Rg_1$ interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Conclusion: Ginsenoside $Rg_1$ can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.

• Journal of agricultural medicine and community health
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• v.18 no.2
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• pp.105-119
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• 1993

The purpose of this study was to evaluate the program for the control of acute respiratory infections(ARI) in children in a Korean rural area(Yonchon county). Evaluating the program, we focused on the pattern of prescription and appropriateness of antibiotics prescribed by the health personnel who had participated in the ARI Control Program. It was implemented at the primary health care setting in rural area, such as district hospital, health subcenters, and health posts. During six-months programme monitoring period, medical records were reviewed and collected data were analysed by the pediatrician, research coordinator of this study. The baseline data were collected from medical records of the same period(six months) of one year before the implementation of the ARI programme. The study results were as follow : 1. Common cold was the most prevalent disease(78.7%. 594 cases) among the all ARI cases (755 cases). The less frequent cases were bronchitis(11.9%), acute pharyngitis(5.2%), and pneumonia(1.8%). 2. Significant reduction in the use of antibiotics was observed after the programme implementation. Ninety three(15.7%) of 594 common cold cases were received antibiotics compared with 282(35.2%) of 802 in the baseline period. In the cases of bronchitis and acute pharyngitis, the reduction rates were 15.1% and 23.2% respectively compared to the baseline period. 3. Mean duration of antibiotics prescription was 1.81-1.75 days, similar to the baseline data. 4. The appropriateness rate of antibiotics prescriptions were 84.3%(common cold), 35.6% (bronchitis) and 28.2%(acute pharyngitis). In the case of pneumonia, the antibiotics prescription was compatible to the criteria developed. 5. Pediatrician prescribed antibiotics more appropriately for all cases than general practitioners in health sub-center, and nurse practitioners in health posts. 6. Antibiotics therapy was shown to be of no effect in the treatment of the all ARI cases. At the 5 and 10 days check-up of common cold cases after visits, proportion of improved patients were 58.3% in the antibiotics-used group and 51.4% in the control group. In the other cases of ARI, the patterns of response were similar to common cold. None of the differences in outcome between the antibiotics-used and control group was statistically significant. This ARI programme may have substantial a substantial impact on antibiotics use at the public health institutions(district hospital, health subcenters, health posts) which are of major domain for primary health care in Korean rural areas.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5311-5316
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• 2014

Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.135-147
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• 2008

Objectives: Oriental pear was used as traditional remedies for respiratory diseases like cough and asthma etc. The purpose of this study was to observe the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs. Methods: In order to study the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization for 10 days and 20days. And 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The experimental groups were divided 6groups(10d1P, 10d2P, 10d4P, 20d1P, 20d2P and 20d4P) by meditation quantity and period. We measured isometric contractile responses to acetylcholine(ACh) and KCl in the isolated tracheal smooth muscle(TSM), IL-4, eosinophil and lymphocyte in bronchoalveolar lavage fluid(BALF), IgE in serum, WBC, RBC and hemoglobin in blood. Results: Contractile responses of TSM to ACh, the sensitivity of TSM to Ach and the maximal contractile response of TSM to KCl were decreased by direct proportion of meditation quantity. Eosinophil and IL-4 level in BALF were more significantly decreased, and IgE level in serum was more significantly increased in 10d4P and 20d4P group than the control group. Conclusions: Based on the above results, it is assumed that oral administration of the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) can help the preventing effects of allergic asthma.