• Radiation Oncology Journal
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• v.22 no.1
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• pp.25-32
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• 2004

Purpose : Evaluate the efficacies and toxicities of concurrent chemoradiotherapy (CCRT), with or without intraluminal brachytherapy (ILB), using a retrospective analysis in esophageal carcinomas with respect to survival. Materials and Methods : From April 1995 to July 2001, a total of 65 patients, diagnosed with an esophageal carcinoma, were treated by CCRT, with 21 also treated by ILB after CCRT. External radiotherapy was peformed using 6 or 10 MV X-rays, with a dose range of $46.8~\69.6$ Gy (median; 59.4). The ILB was peformed using high-dose-rate brachytherapy with Ir-192. The fractionation of ILB was 3 Gy by 4, or 5 Gy by 2 fractions. Cisplatin $(75\;mg/m^2)$ was given on each first day of weeks 1, 5, 9 and 13, and 5-FU $(1,000\;mg/m^2)$ as a continuous infusion for the first 4 days of each course. Results : The median survival time of all patients was 15 months, and the 1, 2 and 3-year survival rates were 55.4, 29.2 and $20.7\%$, respectively. The 2-year survival rates of the patients with and without ILB were 33.3 and $27.3\%$, respectively (p=0.80). The 2-year survival rates of the patients with a complete, partial and no response were 44.1, 13.8 and $0\%$, respectively (p=0.02). The response to treatment was the only significant factor affecting the overall survival from a multivariate analysis. Conclusion : This study has shown that the survival outcomes of CCRT were much better than previous results with radiotherapy alone. However, the addition of ILB after CCRT showed no advantage over that of CCRT alone.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

• Journal of Microbiology and Biotechnology
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• v.18 no.9
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• pp.1606-1612
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• 2008

Interleukin (IL)-32 is a recently identified proinflammatory cytokine that is one of the IL-18 inducible genes, and plays an important role in autoimmune and inflammatory diseases. We produced antibodies against IL-32 and studied the expression of IL-32 in human stomach cancer. We detected IL-32 secreted from K-562 cells which were stably transfected with IL-32 and in the sera of stomach cancer patients by a sandwich ELISA using a monoclonal antibody KU32-52 and a polyclonal antibody. In order to optimize a sandwich immunoassay, recombinant IL-32a was added, followed by the addition of a biotinylated KU32-52 into microtiter plate wells precoated with a goat anti-IL-32 antibody. The bound biotinylated KU32-52 was probed with a streptavidin conjugated to HRP. This sandwich ELISA was highly specific and had a minimal detection limit of 80 pg/ml (mean${\pm}$SD of zero calibrator) and measuring up to 3,000 pg/ml. This ELISA showed no cross-reaction with other cytokines such as hIL-1$\alpha$, hIL-1$\beta$, hIL-2, hIL-6, hIL-8, hIL-10, hIL-18, and hTNF-$\alpha$. Intra-assay coefficients of variation were 18.5% to 4.6% (n=10), and inter-assay coefficients were 23% to 9% (n=10). The average IL-32 level in the sera of 16 stomach cancer patients (189 pg/ml) was higher than that of 12 healthy control men (109 pg/ml). Our results indicate that serum IL-32 level can be detected by using an established ELISA, and that this immunoassay and mAb KU32-09 specific for immunohistochemistry can be used in the detection of expressed and secreted IL-32 in stomach cancer patients.

• Journal of Dairy Science and Biotechnology
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• v.33 no.4
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• pp.237-245
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• 2015

The aim of this study was to evaluate physicochemical characteristics of the Mozzarella cheese produced by Streptococcus macedonicus LC743 with immunomodulating activity. The Mozzarella cheese produced by S. macedonicus LC743 has contents of water, protein and fat 53.16%, 53.16% and 20.52%, respectively. In case of nitrogen composition, water soluble nitrogen (WSN), trichloroacetic acid soluble nitrogen (TCASN), phosphotungstic acid soluble nitrogen (PTASN) has the value of 0.384%, 0.051% and 0.060 Nmg/g, respectively. Total amino acid of Mozzarella cheese produced by S. macedonicus LC743 has the higher contents of amino acid than Mozzarella cheese produced by commercial starter except for cysteine. The Mozzarella cheese has immunomodulating activity on IL-$1{\alpha}$, TNF-${\alpha}$, NO with the value of >2,000 pg/mL, 743.38 pg/mL and $8.31{\mu}M$, respectively. The immunomodulating activity of Mozzarella cheese produced by S. macedonicus LC743 was higher than domestic of imported cheese.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.208-214
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• 2018

Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1213-1219
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• 2010

We evaluated the anti-aging potential and safety of black garlic extract for cosmeceutical ingredient. Black garlic was made by spontaneous fermentation for 40 days at $60{\sim}70^{\circ}C$, 85~95% RH without any additives. The 10% black garlic extract had sweet odor, antioxidant activities and inhibitory activities of skin againg enzymes such as tyrosinase and elastase. The skin safety was performed to evaluate of potential toxicity using the primary irritation test and skin sensitization test. The black garlic extract did not show any adverse reactions such as erythema and edema on intact skin sites at primary irritation test, but on abraded sites, some experimental animals showed very slight erythema. So, the black garlic extract was classified as a practically non-irritating material based on the score 0.23 of primary irritation index. The skin sensitization study was tested by the guinea pig maximization test (GPMT) and Freund's complete adjuvant (FCA) with intradermal injection of 10% black garlic extract. The skin sensitization test showed no skin sensitization. The allergic sensitization depends on tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). The concentration of IL-6 on challenged tissue of treated with black garlic extract was not significantly different with negative control group (saline treated group). Based on this study, the potential for black garlic as a cosmeceutical ingredient was proven.

• Journal of Applied Biological Chemistry
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• v.58 no.3
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• pp.241-246
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• 2015

This study was performed to investigate the antiinflammatory activities of taxifolin from Opuntia humifusa. A potent anti-oxidant activity was shown from the leaf extract at $IC_{50}$ value of $38.33{\pm}1.07{\mu}g/mL$ and fruit extract at $IC_{50}$ value of $40.23{\pm}2.21{\mu}g/mL$ by 1,1-diphenyl-2-picrylhydrazyl assay. Fraction of taxifolin from leaf extract identified using high performance liquid chromatography and gas chromatography/mass spectrometry. The results of cell viability indicated that taxifolin did not show cytotoxicity on RAW 264.7 cells at $500{\mu}M$ of concentration. The result showed that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide. In addition, taxifolin inhibited LPS-induced tumor necrosis factor-${\alpha}$ and interleukin-6 production by cytokine assay and cyclooxygenase-2 expression by western blot analysis, meaning taxifolin has a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa showed anti-inflammatory activities.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.287-318
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• 2000

The purpose of this study is to observe the effect of Aqua-acupuncture utilizing Lycopi Herba Solution(LH-AS) on arthritis. For that purpose, we formed three experimental group, synovial cells of human body, normal BALB/C mice and DBA/1J mice with collagen II-induced arthritis, and measured the treatment effect of LH-AS on each group. The conclusions are as follows. 1. After the LH-AS treatment on synovial cells, there were no significant change in 1, 10, 50 and $100{\mu}g/m{\ell}$ whereas there was significant change in 200 and $400{\mu}g/m{\ell}$ in cytotoxicity. 2. IL-6, IL-$1{\beta}$, TNF-${\alpha}$ gene expression of synovial cells and the secretion amount of IL-6 and IL-$1{\beta}$ are significantly inhibited in treatment group with LH-AS. 3. The proliferation of synovial cells was significantly inhibited in treatment group with rIL-6, LH-AS 200 and rIL-6, $100{\mu}g/m{\ell}$. 4. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the incidence of arthritis, hind paw edema, the index of arthritis and DTH were significantly inhibited. 5. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, splenetic weight was significantly increased and the number of leukocyte was significantly decreased. But there was no significant change in the number of platelet. 6. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the number of $CD4^+$, $CD8^+$ activated cells and the surface-receptor expression were significantly increased whereas the number of $CD19^+$ activated cells and the surface-receptor expression were decreased. 7. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, total protein, LDH were significantly decreased, but there was no significant change in creatinine. 8. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, it was observed that the adherent cells were morphologically activated and IL-12 and IFN-${\gamma}$ gene expression were increased. 9. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, the number of $CD4^+$, $CD8^+$, $CD19^+$ activated cells and surface-receptor expression were inhibited when being compared with the control group. Taking all these observations into account, LH-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• The Korea Journal of Herbology
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• v.23 no.2
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• pp.179-192
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• 2008

Objectives : Draconis Resina (DR) has been used as a traditional Korean herbal medicine since ancient times, and today it is used as a medication for wounds, tumors, diarrhea, rheumatism, in the itching of insect bites and with other conditions in the folk medicine. The aim of this study was to determine whether fractionated extracts of DR inhibit free radical generation, intracellular oxidation, production of nitrite, an index of NO, PGE2, iNOS, COX-2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, Methods : DR extract prepared with methanol, and then fractionated with hexane, dichloromethane, ethylacetate, n-butanol and water. Inhibitory effect of DR onto free radical generation was determined by measuring DPPH, superoxide anions and nitric oxide scavenging activities in vitro. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Intracelluar oxidation was analysed by DCF-DA assay. The nitric oxide (NO) production was measured by Griess reagent system. The levels of iNOS and COX-2 expression were confirmed by western blot. And proinflammatory cytokines were measured by ELISA kit. Results : Our results indicated that fractionated extracts, especially dichloromethane and ethyl acetate extracts, significantly inhibited free radical generation, the LPS-induced H202, NO, PGE2 production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 formation in macrophages. Conclusions : Our results indicate that dichloromethane and ethyl acetate extracts of DR have potential as an agent of chronic inflammatory diseases.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.682-692
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• 2012

Sea Buckthorn (Hippophae rhamnoides L.) has been used in traditional medicine for the treatment of cough, indigestion, circulatory problems and pain. The associated anti-inflammatory effect of this agent is achieved via the inhibition of Nf-${\kappa}B$ signaling, a property that has been demonstrated to effectively control the symptoms of various skin disorders, including atopic dermatitis. Accordingly, the purpose of this study was to assess the efficacy of Sea Buckthorn in reducing the production of lipopolysaccharide (LPS) activated nitric oxide (NO) by inhibiting the Nf-${\kappa}B$ pathway, as measured by the symptoms of atopic dermatitis (AD) occurring secondarily to inflammation and immune dysregulation. Our data demonstrate that Sea Buckthorn significantly decreased the LPS-induced production of NO (p<0.001). Atopic dermatitis was induced by repeated application of 2,4-dinitrochlorobenzene to the dorsal skin of mice. Topical application of 5% Sea Buckthorn extract improved the symptoms of AD, specifically reducing disease severity scores, scratching behaviors and epidermal thickness. When compared to the control group, animals treated with Sea Buckthorn exhibited increased serum IL-12 levels and decreased serum TNF-${\alpha}$, IL-4 and IL-5 levels. Such a modulation of biphasic T-helper (Th)1/Th2 cytokines may result in a reduction in serum IgE levels. Our findings suggest that mechanism of action of Sea Buckthorn in the treatment of AD is associated with a marked anti-inflammatory effect as well as an inhibition of Th2-mediated IgE overproduction via the modulation of biphasic Th1/Th2 cytokines. Such results suggest that topical Sea Buckthorn extract may prove to be a novel therapy for AD symptoms with few side effects.