• Microbiology and Biotechnology Letters
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• v.40 no.1
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• pp.50-56
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• 2012

The Wnt/${\beta}$-catenin signaling pathway regulates diverse developmental processes and adult tissue homeostasis. Inappropriate regulation of this pathway has been associated with human diseases, such as cancers, osteoporosis, and Alzheimer's disease. Using a cell-based chemical screening with natural compounds, we discovered silybin, a plant flavonoid isolated from the Silybum marianum, which activated the Wnt/${\beta}$-catenin signaling pathway in a synergy with Wnt3a-conditioned medium (Wnt3a-CM). In the presence of Wnt3a-CM, silybin up-regulated ${\beta}$-catenin response transcription (CRT) in HEK293-FL reporter cells and 3T3-L1 preadipocytes through stabilization of intracellular ${\beta}$-catenin protein. Silybin and Wnt3a-CM synergistically reduced expression of important adipocyte marker genes including peroxisome-proliferator-activated $receptor{\gamma}$ ($PPAR{\gamma}$) and CAATT enhancer-binding protein ${\alpha}$ (C/$EBP{\alpha}$) in 3T3-L1 preadipocytes, accompanied by the activation of Wnt/${\beta}$-catenin signaling pathway. Taken together, our findings indicate that silybin is a small-molecule synergist of the Wnt/${\beta}$-catenin signaling pathway and can be used as a controllable reagent for investigating biological processes that involve the Wnt/${\beta}$-catenin signaling pathway.

• Journal of The Korean Dental Society of Anesthesiology
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• v.14 no.2
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• pp.101-106
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• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.367-375
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• 1998

Purpose : Xerostomia is a complication met by almost all patients who have radiotherapy for cancers of head and neck. Many studies for prevention of xerostomia will be necessary. Radiation-induced acute response of salivary glands has been defined as interphase death or apoptosis. Increased intracellular calcium level have an important role in radiation-induced apoptosis. Calcium channel blocker may prevent radiation-induced apoptosis of salivary glands. This study was designed to evaluate the effectiveness of diltiazem known as calcium channel blocker and pentoxifylline with inhibition of inflammatory response on the apoptosis as an acute response of radiation in rat salivary glands. Materials and Methods : Sprague-Dawley rats with about body weight 200-250 g were divided into 5 study groups : control, radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation. The diltiazen and pentoxifylline were injected intraperitoneally 20 mg/kg and 50 mg/kg, 30 and 20 mimute before irradiation. respectively. Irradiation was given with a 4 MV linear accelerator. The 1600 cGy of radiation was delivered in a single fraction through a single anterior portal encompassing the entire neck. After 24 h of irradiation, rats were sacrificed and parotid and submandibular glands were removed and stained with hematoxylin and eosin. The quantification of apoptosis was performed by microscopic examination of stained tissue sections at a magnification of 200X and the percentage of apoptotic cell was calculated. Results : On parotid glands, the percentage of apoptosis by radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.72$\%$ (8.35/486), 0.64$\%$ (2.9/453), 0.23$\%$ (1.2/516), and 0.28$\%$ (1.1/399), respectively. The apoptosis was markedly reduced in the groups receiving drugs compared with groups receivinge, radiation alone (p<0.05). In serous cell of submandibular glands, the percentages of apoptosis of radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.94$\%$ (l1/567), 0.34$\%$ (1.9/554), 0.28$\%$ (1.8/637), and 0.22$\%$ (1.3/601), respectively. In the mucus cell of submandibular glands, the percentages of apoptosis were 0.92$\%$ (5.1/552), 0.41$\%$ (2.5/612), 0.29$\%$ (1.3/455), and 0.18$\%$ (1.0/562), respectively. The apoptosis was markedly reduced in the serous glands (p<0.05), but there was no difference in development of apoptosis in each group of mucus gland. Conclusion : These results suggest that radiation-induced apoptosis of serous cells of salivary glands may be decreased by diltiazem and pentoxifylline administration.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.136-141
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• 2001

Purpose : To evaluate the significance of serum SCC for the monitoring of treatment response and the early detection of distant metastasis during radiotherapy (RT). Materials and Methods : In 13 patients with histologically proven primary squamous cell carcinoma of uterine cervix, serum SCC values were checked in pre-RT point, weekly during RT, and in post-RT point. Results : In 4 of 13 cases, metastasis appeared at the end of external RT, so that intracavitary radiation couldn't be peformed.01 these 4 cases,3 with elevated pre-RT SCC level, who resulted in lung metastasis on chest PA at the end of external RT showed decreased post-RT SCC value despite of metastasis. Of all 10 cases with elevated pre-RT SCC value (including 3 with metastasis at the end of external RT), SCC value was higher than pre-RT value in 7 at 9 Gy and the difference was statistically significant. At 18 Gy, SCC was higher in 4 and lower in 6 than pre-RT value. After 18 Gy, SCC value decreased continuously to the end of RT in all 10 cases. Conclusion : During RT, SCC value increased initially at 9 Gy. To 18 Gy, SCC value decreased to the nearly same with pre-RT value. After 18 Gy, to the end of RT, SCC value decreased continuously and normalized in completely responded cases. In cases with appearance of lung metastasis, SCC value also decreased with the disappearance of main mass of uterine cervix despite metastasis.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.135-146
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• 2001

Background : One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance T AA release by cell destruction, as well as the cytokine genes for immune cell attraction. Methods : We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK$\pm$ad-GM-CSF$\pm$ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts. Results : LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen. Conclusion : It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.

• Korean Journal of Food Science and Technology
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• v.30 no.4
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• pp.976-982
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• 1998

The effects of the glycoprotein (PAG) isolated from Pteridium aquilinum on the immune function was examined in mice. PAG was intraperitoneally administered into BALB/C mice for 14 days and the antibody forming ability to hen egg lysozyme (HEL) and the blastogenic responses of splenocytes were measured. PAG treatment significantly increased antibody formation to HEL in a dose-dependent manner. Blatogenesis of splenocytes in response to lipopolysaccharide (LPS, B-cell specific mitogen) or phytohemagglutinin (PHA, T-cell specific mitogen) was also increased after treatment with PAG, indicating that the PAG increases both humoral and cellular immunities. To examine whether the immune function of PAG was via a direct effect on the lymphocytes, splenocytes were isolated from BALB/C mice, exposed to various concentrations of PAG in vitro and the blastogenic responses were measured. In vitro exposure to PAG significantly increased blastogenesis of splenocytes to LPS up to $500{\;}{\mu}g/kg$, whereas the blastogenic response to PHA was not altered by PAG treatment. To identify the fraction responsible for the increase in the immune function, the effect of periodate digest, pronase digest or purified polysaccharide on the antibody production to HEL was examined. Crude protein fraction of PAG significantly increased the antibody formation to HEL. On the other hand, both crude and purified polysaccharide fractions did not have any effects on the antibody production ability. These data indicated that 1) PAG increased both humoral and cellular immune functions, 2) the increase in humoral immunity was probably via a direct action of PAG on lymphocytes and 3) the protein portion of PAG was responsible for the increase in humoral immunity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.298-305
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• 2017

Atopic dermatitis is a chronic, relapsing inflammatory skin disease. This study aimed to investigate the therapeutic benefits of Aronia melanocarpa (AM) and Moringa oleifera seed extract (MO) on experimental atopic dermatitis. We examined the effects of AM or MO and their combination on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in BALB/c mice as well as tumor necrosis factor $(TNF)-{\alpha}$ and interferon $(IFN)-{\gamma}-stimulated$ HaCaT keratinocytes. Mice were orally treated with extract during repeated application of DNCB to shaved dorsal skin. Our results show that treatment with AM and MO in combination reduced histological manifestations such as epidermal hyperplasia and inflammatory cell infiltration. Furthermore, it significantly decreased skin thickness and serum immunoglobulin E (IgE) level compared to the AM or MO alone treated group. Combined extract of AM and MO suppressed expression of $TNF-{\alpha}/IFN-{\gamma}-induced$ T helper 2 (Th2) chemokines such as thymus and activation-regulated chemokine and macrophage-derived chemokine. To sum up, combination of AM and MO suppressed the inflammatory response and serum IgE as an indicator of several allergic diseases in DNCB-induced experimental atopic dermatitis and Th2 chemokine expression in HaCaT cells. This result suggests that combination of AM and MO could be a valuable strategy to improve atopic dermatitis.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.51-57
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• 2006

Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

• Journal of radiological science and technology
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• v.8 no.2
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• pp.47-63
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• 1985

This paper was aimed to study the effects of Cobalt-60 gamma ray irradiation on Albino rat blood cells and the activity of enzymes were measured using blood cell auto analyzer (Cell-Dyn 900) and enzyme autoanalyzer (Gilford 3500) respectively. Cobalt-60 gamma rays those are grouped into 200R, 400R, 600R, 800R, 1,000R, 1,200R, 1,300R, 1,400R, 1,500R and 1,600R to the rats of male and female and measured the numeral varieties of blood corpuscles of the rats and the active varieties of enzyme of acid, alkaline phosphatase (ACP, ALP), lactic acid dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase. (GPT) those came out after 1, 3, 5 or 7 days. The results are summarized as follows: 1. In both case of male and female, the numeral varieties of the erythrocytes, in the 200R group of irradiation showed the minimum value in the 3 days group and a tendency of increase in the 5 and 7 days groups, while the numeral varieties of the leucocytes in every groups of irradiation showed a tendency of a rapid decrease after a day. The numeral varieties of the blood platelet in both case of male and female didn't show generally any great change in a day and 3 days groups, but showed a rapid decreasing appearance after the 5 days. 2. In both case of male and female, the activities of ACP were on the decrease gradually after 3 days of the irradiation and the activities of ALP were on the decrease after 5 days. Similarly in both case of mate and female, the activities of LDH showed the decrease after 3 and 5 days, and the phenomenous of GOT showed an appearance of increase in a day, but decreased after 3 days. As for the GPT activities couldn't find any great change in the male rats in comparison with the control groups, but in the female rats a tendency of the increase in 600R, 800R, 1,000R groups after 3 days. 3. In the case of the irradiation of high quantity of ray more than 1,200R, all rats died after 4 days, and by the irradiation of 1,600R all rats died after 3 days, and it showed the sensitive response of a living body to the irradiation of high quantity.