• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• Journal of Life Science
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• v.28 no.8
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• pp.992-998
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• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• The Microorganisms and Industry
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• v.15 no.2
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• pp.2-7
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• 1989

Waksman과 Heinrich(1943)에 의해 Streptomyces속이 기술되고 actinomycin, streptomycin등의 많은 항생물질이 발견되면서 방선균(actinomycetes)은 산업적으로 중요한 미생물이 되어 왔으며, 근래에는 항생물질 뿐만 아니라 효소, 효소저해제, 면역조절물질 등 소위 생리활성물질(bioactive compound)의 생산균으로서 주목을 받고 있다. 그러나 지금까지 대부분의 스크리닝이나 연구의 대상은 주로 중성 pH에서 잘 자라는 호중성 방선균(neutrophilic actionmycetes)이었지만 산성이나 알칼리성 토양, 고온, 고열, 고압 등과 같은 특수환경에서 분리된 균주나 희귀 방선균(rare actinomyces)에 대한 관심도 점점 높아지고 있다. 산성 토양에서 분리된 방선균에 관한 연구는 Jensen(1928)의 연구로부터 시작하였지만 Lonsdale(1985)이 침엽수림, 산성탄광 등에서 분리된 방선균을 수리분류할 때까지 활발하게 이루어지지 못하였다. 본 고에서는 호산성 방선균위 분포, 생리적 특성, 수리분류학적 연구, 화학적 분류(chemotaxonomy), 산업적 응용가능성 등을 살펴보고자 한다.

• Journal of Life Science
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• v.34 no.10
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• pp.744-754
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• 2024

Cancer cells exhibit a unique metabolic process for uncontrolled cell division, providing bioenergy and intermediates, which are significantly different from normal cells. Here an aerobic glycolysis converts most of the pyruvate produced from glucose into lactate and inefficiently produced ATP. Cancer cells counter their lack of energy through glutamine metabolism, together with glucose. Glutamine is the most abundant amino acid in the blood and is used for the synthesis of amino acids, nucleotides, and lipids, as well as bioenergy through glutaminolysis. Cancer cells rely on glutamine rather than normal cells, showing more than half of the tricarboxylic acid cycle metabolites derived from glutamine, called glutamine addiction. Oncogenes c-Myc also regulates the expression of various genes involved in glutamine metabolism and promotes the absorption of glutamine. Whether glutaminase (GLS) causes or inhibits tumors is controversial. However, GLS1 is a promising treatment target due to its higher carcinogenic incidence, whereas GLS2 is known to act as a tumor suppressor. The 4th-generation metabolic anti-cancer therapy, which has been actively investigated since the mid-2010s, is based on a complex and sophisticated network of cancer metabolites. These drugs directly regulate the energy metabolism of cancer cells to maximize anti-cancer effects without side effects. GLS is a crucial enzyme for cancer metabolism and tumor progression that catalyzes the first stage in the process of glutaminolysis. The development of anti-cancer drugs targeting GLS enzymes has emerged as a promising strategy.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Ginseng Research
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• v.27 no.2
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• pp.47-51
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• 2003

Synergistic anticancer activities of red ginseng acidic polysaccharide (RGAS) showing immunomodulatory activity were evaluated by combined treatment with anticancer agents such as Cyclophosphamide (CY) or 5-Fluorouracil (5-FU) in experimental tumor models. The combined treatment of RGAP (100 mg/kg) and CY (3 mg/kg) exhibited 71% of survival rate in lift span of sarcoma 180-bearing mice, while single treatment of RGAP (100 mg/kg) and CY (3 or 10 mg/kg) exhibited 43, 14 and 43% of survival rates, respectively. In addition, when RGAP (100 mg/kg) was administered in combination with 5-FU (2.5 mg/kg) to sarcoma 180 tumor-bearing mice, higher survival rate was found when compared with RGAP or 5-FU treatment alone. Moreover, tumor weights in LL/2 lung carcinoma-bearing mice treated combined with RGAP (100 mg/kg) and 5-FU (5 or 10 mg/kg) was obviously decreased when compared with 5-FU alone. These results suggest that clinical trials of RGAP as an adjuvant in cancer chemotheraphy can be higly feasible.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1279-1282
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• 2009

Hepatomegaly and liver dysfunction might develop in patients with diabetes mellitus due to glycogen deposition or nonalcoholic steatohepatitis. We experienced a case of hepatic glycogenosis in a patient with type 1 diabetes mellitus who presented with recurrent hypoglycemia, suggesting impairment of glycogenolysis and gluconeogenesis. A 10-year-old girl with a 4-year history of type 1 diabetes mellitus was admitted because of recurrent hypoglycemia and abdominal pain in the right upper quadrant. She had Cushingoid features and hepatomegaly that extended 6 cm below the right costal margin. Laboratory data and radiologic examination revealed elevated liver enzyme levels due to fatty liver. Periodic acid-Schiff (PAS) staining revealed intense glycogen deposition in the cytoplasm of the hepatocytes and PAS reactivity was lost with diastase treatment. At 2 months after administration of glucagon injection and uncooked cornstarch between meals and at bedtime, the hypoglycemic episodes and liver dysfunction improved. It is important to distinguish hepatic glycogenosis from steatohepatitis, because it is possible to prevent excessive hepatic glycogen storage in hepatic glycogenosis cases by strictly controlling blood glucose level and by glucagon administration. To prevent severe hypoglycemic symptoms accompanied by hepatic glycogenosis, we suggest that uncooked cornstarch, which is effective in maintaining blood glucose level, can also be administered.

• Journal of Periodontal and Implant Science
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• v.33 no.3
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• pp.331-340
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• 2003

본 연구의 목적은 인간의 동맥경화증에서 Porphyromonas gingivalis (P. gingivalis)와 인체 열충격단백 60의 T-세포 및 교차성 B-세포 epitope를 규명하고 수립된 T-세포주의 T-세포 주요조직적합체 양상을 파악하려는 데 있다. P. gingivalis 열충격단백-반응성 T 세포주와 환자의 혈청을 이용하여 P. gingivalis 열충격단백60 분자를 구성하는 104개의 중복성 합성 펩타이드의 T-세포 epitope과 B-세포 epitope을 규명하였다. 인체 열충격단백60에 대한 B-세포 epitope도 같은 방법으로 파악하였다. P. gingivalis, P. gingivalis 열충격단백60 또는 인체 열충격단백60에 대한 IgG 항체는 모든 동맥경화증 환자에서 상승하였다. P. gingivalis 열충격단백60의 3, 15, 24, 33, 45, 53, 64, 84, 88, 99번 펩타이드가 주요한 T-세포 epitope였고 이것들은 T-세포 및 B-세포 공동 epitope이기도 했다. 또한 인체 열충격단백60 교차반응 B-세포 epitope은 15, 29, 53, 56, 69, 74번 펩타이드로 판명되었다. 대부분 환자의 주요조직적합체는 $HLA-DRB1^{\ast}1504$와 $HLA-DZB1^{\ast}0603$으로 나타났다. 결론적으로 P. gingivalis 열충격단백60은 제 2급 주요조직적합제-제한적으로 분해되고 전달되었으며 이 단백질이 공통적인 T-세포 및 B-세포 epitope를 가지면서 동시에 인체 열충격단백60과 교차성 B-세포 epitope을 가지면서 동맥경화증의 면역조절기능에 관여한다고 볼 수 있다.

• 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 Life Science
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• v.30 no.12
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• pp.1070-1077
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• 2020

Treatment with anticancer drugs changes the expression of multiple genes related to cell proliferation, migration, and drug resistance. These changes in gene expression may be connected to regulatory networks for each other. This study showed that doxorubicin treatment induces the expression of oncogenic FosB and decreases the expression of oncogenic SETDB1 in A549 and H1299 human lung cancer cells, which are different in tumor suppressor p53 status. However, a small difference was detected in the quantitative expression of those proteins in the two kinds of cells. To examine the potential regulation of SETDB1 and FosB by p53, we predicted putative p53 binding sites on the genomic DNA of SETDB1 and FosB using a TF motif binding search program. These putative p53 binding sites were identified as 18 sites in the promoter regions of SETDB1 and 21 sites in the genomic DNA of FosB. A luciferase assay confirmed that p53 negatively regulated the promoter activities of SETDB1 and FosB. Furthermore, the results of RT-PCR, western blot, qPCR, and immunostaining experiments indicated that the transfection of exogenous p53 decreases the expression of SETDB1 and FosB in H1299 cells. This indicates that p53 negatively regulates the expression of SETDB1 and FosB at the transcriptional level. Collectively, the downregulation of SETDB1 and FosB by p53 may provide functional networks for apoptosis and for the survival of cancer cells during anticancer drug treatment.