• 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.

• Journal of Life Science
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• v.29 no.8
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• pp.922-940
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• 2019

Obesity, represented by abnormal fat accumulation due to an imbalance between energy intake and expenditure, is a major public health issue worldwide, leading to multiple noncommunicable diseases, including atherosclerosis, hypertension, type 2 diabetes, and cancer. Diverse solutions have been proposed to combat obesity. Attention has focused on two types of adipose tissues as a promising therapeutic target in obesity: traditional brown and beige or brite. Unlike energy-storing white adipose (endocrine) tissue, traditional brown adipose tissue and beige adipose tissue have energy-dissipating thermogenic properties. Both types of tissue are present in adult humans and inducible through external stimuli, such as cold exposure, ${\beta}3$-adrenergic receptor agonists, and phytochemicals. Among these stimuli, microbiota present in the human intestinal tract participate in multiple metabolic activities. Modulation of gut microbiota may offer a potent and possibly curative strategy against various metabolic diseases. Numerous studies have focused on the effects of established antiobesity treatments on the gut microenvironment or brown-adipose-tissue activation. In this review, we focus mainly on stimuli known to alleviate obesity, weight gain, and metabolic diseases, in addition to known and possible inter-relations between gut microbiota modulation and similar interventions and adipose tissue browning. The findings may pave the way toward new strategies against obesity.

• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.164-171
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• 2019

Radiation therapy has many side effects, such as digestive mucosal ulcers, without regard to its efficacy. The purpose of this study is to address an alternative method to replace the limitation of radiation therapy using radiomimetic microbial ribotoxins. In the evaluation of cancer therapy, we analyzed the formation of colorectal cancer (CRC) cell spheroids, which can take into account the heterogeneous cellular constitution, tumor stem cells, and the surrounding microenvironment. Ribotoxic stress interfered with the spheroid structure composed of relatively small clusters. Spheroids under ribotoxic stress were structurally sparse and their shrinkage was very slow. In the control group, the clusters of strongly aggregated cells were resistant to physical stress, but the ribotoxic stress-exposed spheroids were easily broken up by the physical stress. Moreover, the ribosome-insulted CRC cells slowly migrated to form clusters and the cell-cell junctional points in the ribosome-insulted spheroids were rarer than those in the control CRC spheroid. Moreover, levels of the cell-to-cell junctional protein E-cadherin were suppressed by ribotoxic stress in both allograft and xenograft spheroids. In conclusion, the radiomimetic microbial ribotoxins induced structural defects in CRC cell spheroids via retardation of migration and cell-cell junction in the formation of three-dimensional structures, and provides a basis for the mechanism of pharmacological radiomimetic anticancer actions as an alternate to radiotherapy against cancer.

• Journal of Life Science
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• v.29 no.5
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• pp.530-536
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• 2019

Glioblastoma (GBM) is the most incurable brain cancer derived from the transformed glial cells. Standard anti-GBM treatment, including surgery and chemoradiotherapy, does not ensure good prognosis for the patients with GBM, because successful therapy is often impeded by presence of glioma stem cells (GSCs). GSCs, which is generally divided into proneural (PN) and mesenchymal (MES) subtype, are understood as subpopulation of cancer cells responsible for GBM initiation, progression and recurrence after standard treatments. In the present study, we demonstrate that PN subtype GSCs differentially transit to MES subtype GSCs by specific cytokines. The expression of CD44, a marker of MES subtype GSCs, was observed when GSC11 PN subtype GSCs were exposed to tumor necrosis factor alpha ($TNF-{\alpha}$) cytokine and GSC23 PN subtype GSCs were treated to transforming growth factor beta 1 ($TGF-{\beta}1$) cytokine. Ivy glioblastoma atlas project (Ivy GAP) bioinformatics database showed that $TNF-{\alpha}$ and $TGF-{\beta}1$ were highly expressed in necrotic region and perivascular region, respectively. In addition, $TNF-{\alpha}$ signaling was relatively upregulated in necrotic region, while $TGF-{\beta}$ signaling was increased in perivascular region. Taken together, our observations suggest that MES subtype GSCs can be derived from various PN subtype GSCs by multimodal cytokine stimuli provided by neighboring tumor microenvironment.

• Korean Journal of Environment and Ecology
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• v.35 no.1
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• pp.37-47
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• 2021

This study carried out the plant sociological survey of Abies nephrolepis forest in Mt. Seorak, which is in danger of deterioration due to the accelerated climate change. We examined seventy quadrats obtained from the survey and used the TWINSPAN technique to classify communities. We then performed the DCA method for the sequence analysis and analyzed the characteristics of each community. A. nephrolepis forest of Mt. Seorak is composed of four communities (A. nephrolepis-Lonicera caerulea var. edulis community, A. nephrolepis-Acer komarovii community, A. nephrolepis-Ac. pseudosieboldianum community, and A. nephrolepis-Betula costata community). Each community showed a different distribution according to location because different microenvironments are formed depending on location such as altitude and slope direction, resulting in different species composition. Each community showed differences in environmental characteristics such as altitude, rock ratio, soil characteristics, and litter layer thickness. As a result, there were significant differences between communities in the number of species and individuals, coverage, tree size, and species diversity, as well as differences in species composition. The A. nephrolepis-L. caerulea var. edulis and A. nephrolepis-Ac. komarovii communities were located in high altitude with high rock ratios and had little development of tree layer. On the other hand, the A. nephrolepis-Ac. pseudosieboldianum and A. nephrolepis-B. costata communities were relatively in low altitude with high soil ratio and had the development of tree layer with high species diversity.

• Journal of Life Science
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• v.33 no.3
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• pp.295-303
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• 2023

Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

• Journal of Life Science
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• v.33 no.8
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• pp.612-622
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• 2023

T-cell deficiency may occur in various clinical conditions including congenital defects, cell/organ transplantation, HIV infection and aging. In this regard, the development of artificial thymus has recently been attracting much attention. To achieve this aim, the development of techniques for 3D culture of thymic stromal cells is necessary because thymocytes grown only in a 3D thymic microenvironment can be differentiated fully to become mature, immunocompetent T cells; the same cannot be achieved for thymocytes grown in 2D. This study aimed to develop a nanotechnology-based 3D culture technique using polymeric scaffolds for thymic epithelial cells (TECs), the main component of thymic stromal cells. Scanning electron microscopic observation revealed that the pores of both PCL and PCL/PLGA scaffolds were filled with TECs. Interestingly, TECs grown in 3D on polydopamine-coated scaffolds exhibited enhanced cell attachment and proliferation compared to those grown on non-coated scaffolds. In addition, the gene expression of thymopoietic factors was upregulated in TECs cultured in 3D on polydopamine-coated scaffolds compared to those cultured in 2D. Taken together, the results of the present study demonstrate an efficient 3D culture model for TECs using polymeric scaffolds and provide new insights into a novel platform technology that can be applied to develop functional, biocompatible scaffolds for the 3D culture of thymocytes. This will eventually shed light on techniques for the in vitro development of T cells as well as the synthesis of artificial thymus.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.242-250
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• 2007

Background: Abnormal angiogenesis can induce hypoxia within a highly proliferating tumor mass, and these hypoxic conditions can in turn create clinical problems, such as resistance to chemotherapy. However, the mechanism by which hypoxia induces these changes has not yet been determined. Therefore, this study was conducted to determine how hypoxia induces changes in cell viability and extracellular microenvironments in an in vitro culture system using non-small cell lung cancer cells. Methods: The non-small cell lung cancer cell line, A549 was cultured in DMEM or RPMI-1640 media that contained fetal bovine serum. A decrease in the oxygen tension of the media that contained the culture was then induced in a hypoxia microchamber using a $CO_2-N_2$ gas mixture. A gas analysis and an MTT assay were then conducted. Results: (1) The decrease in oxygen tension was checked the anaerobic gas mixture for 30 min and then reoxygenation was induced by adding a 5% $CO_2-room$ air gas mixture to the chamber. (2) Purging with the anaerobic gas mixture was found to decrease the further oxygen tension of cell culture media. (3) The low oxygen tension resulted in a low pH, lactic acidosis and a decreased glucose concentration in the media. (4) The decrease in glucose concentration that was observed as a result of hypoxia was markedly different when different types of media were evaluated. (5) The decrease in oxygen tension inhibited proliferation of A549 cells. Conclusion: These data suggests that tumor hypoxia is associated with acidosis and hypoglycemia, which have been implicated in the development of resistance to chemotherapy and radiotherapy.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• The Korean Journal of Ecology
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• v.17 no.3
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• pp.299-310
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• 1994

Intraspecific clonal interactions have important influences on a population structure of the cellular slime mold (CSM). This study was to investigate whether or not evolutionary change in a population could be induced by clonal competition, and to elucidate how various clones in a population evolve in a homogeneous environment of laboratory culture. The characteristic clones of Polysphondylium pallidum which had different resource consumption rates (RCR) and mating types I and II were selected for study. Investigation was conducted for 4 experimental time interval $(T_0-T_4)$; one experimental time interval took almost 10-14 days from inoculation to havest of fruiting bodies. Two sets of 50 clones were cultured from 50 clones at To, and RCR variations of the population were compared between $(T_0\;and\;T_4)$ for each set of clones. Each clone of the CSM had a diverse resource consumption rate, or growth rate, in a homogeneous and limited Cerophyl agar plate despite the passage of 48-56 generations from the beginning of the experiment. Diverse clones with different growth rate could coexist in one site of the homogeneous agar plate as well as heterogeneous soil microenvironment. When there was high clonal diversity of RCR, a clone in a population had high chances to encounter other clones with resultant increased clonal competition. In one set, 26 of 37 clones of mating type I were changed to mating type Il for the 4 experimental time intervals, which indicated that the rate of competitive exclusion among clones during total experiment from $(T_0\;to\;T_4)$ was 0.703. In another set, 31 of 37 clones of mating type I were changed to mating type II , having the rate of competitive exclusion 0.838. The frequency of each of mat~ng types changed by 0.93-1.29% in each successive generation. The competitive exclusion among clones occurred by 1.26-1.75% when approximately $2.6{\times}10^8$ bacterial cells were provided as food and thereafter one generation of myxamoebae of CSM elapsed at room temperature. This finding implicated that in the vegetative state of P, pallidurn there was 1.26-1.75% probabil~ty of evolutionary change per generation changing from one clone to another clone.