• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.4-9
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• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.169-178
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• 2009

DNA immunization induces B and T cell responses to various pathogens and tumors. However, these responses are known to be relatively weak and often transient. Thus, novel strategies are necessary for enhancing immune responses induced by DNA immunization. Here, we demonstrated that co-immunization of influenza virus nucleoprotein (NP) gene significantly enhances humoral and cell-mediated responses to codelivered antigens in mice. We also found that NP DNA coimmunization augments in vivo proliferation of adoptively transferred antigen-specific CD4 and CD8 T cells, which enhanced protective immunity against tumor challenge. Our results suggest that NP DNA can serve as a novel genetic adjuvant in cocktail DNA vaccination.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.946-951
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• 2003

The purpose of this research was to investigate the effect of Maekmoondong-tang(MMDT) on the activity of immune cell. The addition of MMDT(10 ㎍/㎖) enhanced the proliferation of cultured-splenocytes and thymocytes. And administration of MMDT(250, 500 ㎎/㎏) accelerated subpopulation of splenic T lymphocytes in BALB/c mice. In contrast, the treatment of the high concentration (500 ㎎/㎏)of MMDT were decreased thymic T lymphocytes. Administration of MMDT(250, 500 ㎎/㎏) eminently enhanced the production of IFN-γ. And MMDT did not affect the cell viability of Jurkat leukemia cells. These results suggest that MMDT have a immunoregulatory effect via enhanced cell mediated immunity

• Journal of Microbiology and Biotechnology
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• v.16 no.12
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• pp.1919-1927
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• 2006

Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the $p2Ca/L^d$ MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.206-217
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• 2011

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-${\beta}$ treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-${\beta}$ and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-${\beta}1$ and TGF-${\beta}2$. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-${\beta}1$ and TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-${\beta}2$ and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

• Journal of Korean Academy of Nursing
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• v.32 no.5
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• pp.716-726
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• 2002

The purpose of this study was to explore the effects of hand reflexology on the physiological.emotional responses and immunity of the patients with chronic illness. This study looked specifically at patients with chronic renal failure(CRF) and cancer patients. Method: This study was designed as a quasi-experimental nonequivalent control group pre and post test. Subjects were 54 patients who received dialysis and chemotherapy in one hospital. Thirty-one patients were assigned to the experimental group and 23 to the control group. The hand reflexology was applied to both hands of the experiment group for ten minutes each time, 5 times during three days. For data collection, physiological lab levels, immune cells of blood and questionnaires for emotional responses were measured before and after the program. Result: BT of the experiment group was decreased significantly on both of the 1st and the 5th application. PR & BP were decreased significantly on the 1st times, but not 5th times. Hb levels of the experimental group were significantly increased. And emotional responses, vigor and mood scores of the experiment group were significantly increased. B cell & CD19 were increased significantly on the experiment group. Suppressor T cell and NK cell showed significant decrease after the program, but no significant differences between the groups. Conclusion: We have found that the hand reflexology helps the chronic patients to improve physiological.emotional responses and the immune reaction. Through this result, the hand reflexology is effective as a intervention of psychoneuroimmunologic function.

• Journal of Acupuncture Research
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• v.19 no.4
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• pp.56-73
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• 2002

Objective : We need to develop a new treatment method which can curve cancer growth and enhance immunity of patients with various kinds of cancer more safely and effectively, for conventional anticancer treatment has lots of problems to be overcomed, in other words, Its efficacy can be recognizible but it doesn't actually give aid to patients due to its side effects. This study was taken up to evaluate the anticancer and immune-enhancing effect of Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba(SAO) Herbal acupuncture. Methods : SAO Herbal acupuncture solution was made from Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba by decoction. Experimental group was divided into normal(N), control(TC, cancer group induced by S 180), high and low concentration SAO complex Herbal acupuncture group. In the high and low concentration SAO complex Herbal acupuncture group, SAO Herbal acupuncture solution was injected, on the left and right Chok-samni(足三里, ST36) of ICR-male S 180 rats alternatively, by 200mg/kg and 100mg/kg respectively. In vitro, S 180 was cultured with $200{\mu}g$ and $500{\mu}g$ of SAO Herbal acupuncture solution. In each experimental group, we examined the effect of SAO complex Herbal acupuncture on body weight, antitumor, organ weight, activity of macrophage, activity of B cell, spleen cell division, IL-2 production and population of lymphocytes. Results : 1. In Body weight, no significant change was shown, but In solid cancer weight, the high concentration SAO complex Herbal acupuncture group showed signigicant(P<0.05) decrease and significant(P<0.05) increase in the weight of kidney, compared with control group. 2. In activity of macrophage, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, but in vitro, there was no significant increase, compared with control group. 3. In activity of B cell, high and low concentration SAO complex Herbal acupuncture group showed no significant decrease, but in vitro, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, compared with control group. 4. In spleen cell division, high and low concentration SAO complex Herbal acupuncture group had no significant influence on spleen cell division induced by Co A, meanwhile, it was found that macrophge promote spleen cell division in low concentration SAO complex Herbal acupuncture group(P<0.05), compared with control group. 5. In IL-2 production, high concentration SAO complex Herbal acupuncture group showed significant((P<0.05) increase, compared with control group. 6. In population of lymphocytes, high concentration SAO complex Herbal acupuncture group showed significant increase of CD3+(P<0.05), CD4+(P<0.05), CD3+ and CD4+ T cell(P<0.01) and B cell(P<0.05), while low concentration SAO complex Herbal acupuncture group showed significant increase of CD4+(P<0.05), CD8+ T cell(P<0.05) and B cell(P<0.01), compared with control group. Conclusion : SAO Herbal acupuncture inhibited cancer growth and enhanced immunity.

• Reproductive and Developmental Biology
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• v.41 no.3
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• pp.57-63
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• 2017

Xenotransplantation is proposed as a solution to the problem of organ shortage. However, transplantation of xenogeneic organs induces an antigen-antibody reaction in ${\alpha}$-1,3-gal structure that are not present in humans and primates, and thus complement is also activated and organs die within minutes or hours. In this study, we used FasL gene, which is involved in the immune response of NK cell, and US11, which suppresses MHC Class I cell membrane surface expression, to inhibit cell mediated rejection in the interspecific immunity rejection, and also hDAF(CD55) was introduced to confirm the response to C3 complement. These genes were tranfeced into Korean native pig fetal fibroblasts using pCAGGS vector. And cytotoxicity of NK cell and human complement was confirmed in each cell line. The US11 inhibited the cytotoxicity of NK cell and, in addition, the simultaneous expression of US11 and Fas ligand showed excellent suppress to T-lymphocyte cytotoxicity, hDAF showed weak resistance to cytotoxicity of natural killer cell but not in CD8+ CTLs. Cytotoxicity study with human complement showed that hDAF was effective for reducing complement reaction. In this studies have demonstrated that each gene is effective in reducing immune rejection.

• Journal of Acupuncture Research
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• v.23 no.4
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• pp.187-203
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• 2006

Objectives : This study was designed to investigate the antimetastatic and immunomodulating effects of Patriniae Radix. Methods : Acute and subacute cytotoxicity experiment of Patriniae Radix was performed. Antimetastatic experiment was administered in vitro and in vivo. To observe the immunomodulating effects of Patriniae Radix, FACS analysis and ELISA assay were performed. Results : There was no acute and subacute toxicity responses in mouse treated with Patriniae Radix. Antimetastatic experiment in vitro and in vivo showed that Patriniae Radix has antimetastatic effects. This research revealed that Patriniae Radix mediate cellular immunity response. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Conclusion Patriniae Radix Herbal-acupuncture appears to have considerable activity on the treatment of liver metastasis from colon26-L5 carcinoma cell line, and deserves further evaluation in this setting.

• Proceedings of the KIEE Conference
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• 2005.05a
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• pp.72-74
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• 2005

In this paper, we propose an adaptive PID controller using a cell-mediated immune response to improve a PID control performance. The proposed controller is based on the specific immune response of the biological immune system that is cell-mediated immunity. The immune system of organisms in the real body regulates the antibody and the T-cells to protect an attack from the foreign materials like virus, germ cells, and other antigens. It has similar characteristics that are the adaptation and robustness to overcome disturbances and to control the plant of engineering application. We first build a model of the T-cell regulated immune response mechanism and then designed an I-PID controller focusing on the T-cell regulated immune response of the biological immune system. We apply the proposed methodology to building structures to mitigate vibrations due to strong winds for evaluation of control performances. Through computer simulations, system responses are illustrated and additionally compared to traditional control approaches.