• Journal of the Korea Academia-Industrial cooperation Society
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• v.14 no.8
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• pp.3907-3915
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• 2013

Cudrania tricuspidata has been used for a long time as a traditional herb medicine in Korea nad China. This paper has shown the experimental results about the physiological activities of water-, ethanol-, ethyl acetate-soluble fractions from ethanolic extracts of leaves, stems and roots of Cudrania tricuspidata. The effects of these fractions on the growth of various cells have exhibited that the ethyl acetate fractions from leaves, stems and roots inhibited significantly the growths of macrophage(RAW 264.7 cell), melanoma cell(B16-F10 cell), fibroblast cell(CCD-986sk cell), and lung carcinoma cell(A549 cell). The water and ethanol fractions of leaves and ethanol fraction of stems demonstrated better antioxidant activities scavenging radicals than other fractions when compared with the concentrations of different fractions for scavenging free radical DPPH (di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium).

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.1
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• pp.125-143
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• 2007

Purpose : This study was to investigate the anti-inflammatory effects of Kagamsunbanghwalmyungeum(KSBH) which has been medicated the patient such as breast abscess. Methods : In the study of anti-inflammatory effects, KSBH was investigated using cultured cells and a murine models. As for the parameters of inflammation, level of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cell(mLFC) and RAW 264.7 cells. Results : The cytotoxicity on mouse lung fibroblast cells(mLFC) was not served at all concentration of KSBH. KSBH in RAW264.7 cell inhibited IL-l${\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II mRNA genes expression in a concentration-dependent manner, and specially inhibited NOS-II production very significantly at 100${\mu}$g/ ml. KSBH inhibited NO production significantly in a concentration-dependent manner and ROS production in a concentration-dependent manner. KSBH inhibited IL-l${\beta}$, IL-6 and TNF-${\alpha}$ production significantly in serum of acute anti-inflammation-induced mice. KSBH increased the survival rate from the 3rd day on LPS-induced lethal endotoxemia. Conclusion : These results suggest that Kagamsunbanghwalmyungeum(KSBH) can be useful in treating a lot of women mammary diseases caused by inflammation such as breast abscess.

• Journal of Radiation Protection and Research
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• v.34 no.2
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• pp.49-54
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• 2009

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with $^{137}Cs$ $\gamma$-rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and $H_2O_2$-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and $H_2O_2$-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.107-107
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• 2003

The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmium has been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known. Therefore, we undertook the investigation of genes that are induced after cadmium exposure to illustrate the mechanism of cadmium toxicity For this purpose, we employed the polymerase chain reaction-based suppression subtractive hybridization technique. We identified 29 different cadmium-inducible genes in human peripheral mononuclear cells, such as macrophage migration inhibitory factor, lysophosphatidic acid acyltransferase-${\alpha}$, enolase-1${\alpha}$, VEGF, Bax, neuron-derived orphan receptor-1, and Nur77, which are known to be associated with inflammation, cell survival, and apoptosis. Induction of these genes by cadmium treatment was further confirmed by semi-quantitative reverse-transcription polymerase chain reaction. Further, we found that these genes were also induced after cadmium exposure in normal human lung fibroblast cell line, WI-38, suggesting potential use of this induction profile to monitor cadmium toxicity in the lung. Next, Nur77, one of cadmium-inducible genes, was further studied since the products of Nur77 are known to be involved in the apoptotic process of lung cells. Following cadmium treatment, Nur77 gene expression was increased at protein-level in A549 cells. Consistently, the reporter containing Nur77 binding sequence was activated by 2.5-fold after exposure to cadmium in reporter gene analysis by transient transfection experiments. When the plasmid encoding dominant negative Nur77 that represses the transcriptional function of wild-type Nur77 was transfected into A549 cells, the expression of Bax was significantly reduced, suggesting that induction of Nur77 was an important process in cadmium-induced apoptosis in the cells. Cadmium induced the expression of Nur77 in vivo, confirming the relevance of the data obtained in viro. Together our results suggest that Nur77 gene expression in exposure to cadmium leads apoptosis of lung cells which may cause pathological changes in lung.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1284-1289
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• 1998

Synovial sarcoma is a malignant soft tissue neoplasm that occurs frequently in the extremities of young adults, near large joints. The lung is a common site of metastasis but an extremely unusual primary site for synovial sarcoma. We report an unusual case of primary synovial sarcoma that arose in the lung of a 59-year-old woman. The tumor had histologic and immunophenotypic features consistent with biphasic synovial sarcoma These features included of an intimate admixture of cytokeratin and epithelial membrane antigen(EMA)-positive neoplastic epithelial cells and vimentin-positive fibroblast-like spindle cells. The patient had a closed thoracomy drainage and doxycycline pleurodesis for malignant loculated effusion and showed tumor extension in the left whole lung 4 months after pleurodesis. This case is an usual addition to the small number of published reports on primary pulmonary synovial sarcoma The distintive features of this neoplasm allow it to be distinguished from a variety of primary and metastatic malignancies in the lung.

• Tuberculosis and Respiratory Diseases
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• v.86 no.4
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• pp.304-318
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• 2023

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.6
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• pp.556-563
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• 2005

Homogentisic acid was found to scavenge intracellular reactive oxygen species (ROS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and thus prevented lipid peroxidation in human fibroblast (Wl 38) cells. The radical scavenging activity of homogentisic acid was found to protect Wl 38 cells against hydrogen peroxide $(H_2O_2)$ induced oxidative stress, via the activation of extracellular signal regulated kinase (ERK) protein. Homogentisic acid increased the activity of catalase. Hence, from the present study, it is suggested that homogentisic acid protects Wl 38 cells against $H_2O_2$ damage by enhancing the intracellular antioxidative activity.

• Archives of Plastic Surgery
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• v.38 no.3
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• pp.217-221
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• 2011

Purpose: FGF4 (fibroblast growth factor 4) is a newly characterized gene which was found to be a transforming gene in several cancerous cells. FGF4 expression and amplification has been subsequently observed in several human cancers including stomach cancer, breast cancer, head and neck squamous cell carcinoma, lung cancer and bladder cancer. This study was designed to measure the protein expression of FGF4 in malignant skin cancers. Methods: We examined 8 normal skin tissues and 24 malignant skin tumor tissues which were 8 malignant melanomas, 8 squamous cell carcinomas and 8 basal cell carcinomas. The specimens were analyzed for the protein expression of FGF4 using immunohistochemical staining. To evaluate the amount of expression of FGF4, the histochemical score (HSCORE) was used. Results: FGF4 was expressed more intensely in malignant melanoma, followed by SCC and BCC in immunohistochemistry. The average HSCORE was 0.01 for normal skin, 2.02 for malignant melanoma, 1.28 for squamous cell carcinoma, and 0.27 for basal cell carcinoma, respectively. The expression of FGF4 in malignant melanoma and squamous cell carcinoma was increased in comparison with normal tissues and basal cell cancer, and the difference was statistically significant (p<0.05). The difference between malignant melanoma and squamous cell carcinoma was not statistically significant. Conclusion: These findings provide evidences that the expression of FGF4 plays an important role in malignant melanoma and squamous cell carcinoma progressions. This article demonstrates expression of FGF4 in human skin malignant tumors, and suggests that FGF4 is more expressed in highly aggressive skin tumors.

• The Korean Journal of Pesticide Science
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• v.6 no.2
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• pp.96-104
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• 2002

This study was carried out to investigate cytotoxicity of paraquat on NIH 3T3 fibroblasts, toxicity of paraquat and compensatory effects of 3-methylcholanthrene (3-MC) on the rat lung. In order to conduct MIT [3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyl -2H-tetrazolium-bromide] and NR (Neutral red) assay, the $5.0{\times}10^4cell/ml$ of NIH 3T3 fibroblast in each well of 24 multi-dish were cultured. After 24 hours, the cells were treated with solution of paraquat (1, 25, 50 and $100{\mu}M$ respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours. MIT and NR assay were performed to evaluate the cytotoxicity of cell organelles. $MTT_{50}\;and\;NR_{50}$ of paraquat were $1668.97{\mu}M\;and\;1030.85{\mu}M$, respectively. These $IC_{50}$ of Paraquat were decided as a low cytotoxicity by Borenfreund and Puemer (1984). In order to observe the toxicity and compensatory effects of paraquat on the rat lung, Spraque Dawley male rats were used as experimental animals and were divided into paraquat only treated group and simultaneous application group of paraquat and 3-MC, at 30 min and 1, 3, 6, 12, 24, 48 and 96 hrs interval after each treatment. The animals were sacrificed by decapitation and their or the lungs were immediately removed, immersed in fixatives, and were processed with routine method for light microscopic study. Paraffin sections were stained with H&E and iron hematoxylin of Verhoeff. Under the light microscopy, erythrocytes were full in alveolar capillaries at 3 hrs and congested at 24 hrs after paraquat administration. The great alveolar cells (Type II cell) were increased and mitosis of great alveolar were observed in interalveolar septa. Many lymphocytes, macrophages and polymorphonuclear (PMN) cells were observed in connective tissue surrounding lung tissue and germinal center in lymph follicles of terminal bronchiole. Alveolar macrophages were increased in interalveolar septa and alveoli at 48 hrs. And observed many alveolar macrophages at 96 hrs. In iron hematoxylin stain of Verhoeff, Collagen fiber were increased in respiratory bronchiole, interalveolar septa and alveoli and breath of alveoli, and alveolar pore were broaden. But, in paraquat plus 3-MC treated group, morphological changes were mild in lung tissue. These results indicate that 3-MC has a compensatory effects against toxicity of paraquat by conjugation with oxygen.