• The Korean Journal of Urological Oncology
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• 제15권3호
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• pp.103-110
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• 2017

Cancer is the tissue complex consisted with heterogeneous cellular compositions, and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions as well as cell-extracellular matrix play major roles. Conventional cancer models both 2-dimensional and 3-dimensional (3D) present numerous limitations, which restrict their use as biomimetic models for drug screening and fundamental cancer biology studies. Recently, bioprinting biofabrication platform enables the creation of high-resolution 3D structures. Moreover this platform has been extensively used to model multiple organs and diseases, and this versatile technique has further found its creation of accurate models that figure out the complexity of the cancer microenvironment. In this review we will focus on cancer biology and limitations with current cancer models and we discuss vascular structures bioprinting that are critical to the construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinting cancer models and propose future perspectives.

• Biomaterials Research
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• v.22 no.4
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• pp.211-220
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• 2018

Background: Recently, cancer immunotherapy has become standard for cancer treatment. Immunotherapy not only treats primary tumors, but also prevents metastasis and recurrence, representing a major advantage over conventional cancer treatments. However, existing cancer immunotherapies have limited clinical benefits because cancer antigens are often not effectively delivered to immune cells. Furthermore, unlike lymphoma, solid tumors evade anti-cancer immunity by forming an immune-suppressive tumor microenvironment (TME). One approach for overcoming these limitations of cancer immunotherapy involves nanoparticles based on biomaterials. Main body: Here, we review in detail recent trends in the use of nanoparticles in cancer immunotherapy. First, to illustrate the unmet needs for nanoparticles in this field, we describe the mechanisms underlying cancer immunotherapy. We then explain the role of nanoparticles in the delivery of cancer antigens and adjuvants. Next, we discuss how nanoparticles can be helpful within the immune-suppressive TME. Finally, we summarize current and future uses of nanoparticles with image-guided interventional techniques in cancer immunotherapy. Conclusion: Recently developed approaches for using nanoparticles in cancer immunotherapy have enormous potential for improving cancer treatment. Cancer immunotherapy based on nanoparticles is anticipated not only to overcome the limitations of existing immunotherapy, but also to generate synergistic effects via cooperation between nanoparticles and immune cells.

• Journal of Korean Dental Science
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• v.15 no.2
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• pp.121-131
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• 2022

Ameloblastoma is the most representative epithelial odontogenic tumor in the craniofacial region. Through several studies on Ameloblastoma that have been conducted so far, we have been able to get closer to the reality of Ameloblastoma. However, groundbreaking insight into the pathophysiology of Ameloblastoma has not yet been provided. This review assessed three aspects of five recently published papers on Ameloblastoma: cancer stem cells, calcium signaling, and tumor microenvironment, and compared them with previous studies on tumor physiology, including cancer. In addition, the characteristics of Ameloblastoma revealed by the experimental methods presented in the currently published five papers provide the possibility of Ameloblastoma as a study model in general tumor or cancer studies. Furthermore, the mechanisms of action of the chemicals identified in the studies support their potential as candidates for the second-line treatment of Ameloblastoma.

• BMB Reports
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• v.56 no.5
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• pp.287-295
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• 2023

The tumor microenvironment (TME) is a complex system composed of many cell types and an extracellular matrix (ECM). During tumorigenesis, cancer cells constantly interact with cellular components, biochemical cues, and the ECM in the TME, all of which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrate elasticity and biomechanical forces in tumor progression and metastasis. However, the mechanisms underlying the cell response to mechanical signals-such as extrinsic mechanical forces and forces generated within the TME-are still relatively unknown. Moreover, having a deeper understanding of the mechanisms by which cancer cells sense mechanical forces and transmit signals to the cytoplasm would substantially help develop effective strategies for cancer treatment. This review provides an overview of biomechanical forces in the TME and the intracellular signaling pathways activated by mechanical cues as well as highlights the role of mechanotransductive pathways through mechanosensors that detect the altering biomechanical forces in the TME.

• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.356-381
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• 2023

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the blood-brain-barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versus-host disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

• BMB Reports
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• v.57 no.5
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• pp.238-243
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• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.6.1-6.20
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• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2007.05a
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• pp.128-128
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• 2007

• Journal of Ecology and Environment
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• v.38 no.4
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• pp.493-503
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• 2015

This study analyzed how spatial distribution of Himantormia lugubris is affected by the microenvironment in the Antarctic Specially Protected Area (ASPA) No. 171 located in the Barton Peninsula of King George Island that belongs to the maritime Antarctic. In order to determine the population structure of H. lugubris growing in Baekje Hill within ASPA No. 171, we counted the individuals of different size groups after dividing the population into 5 growth stages according to mean diameter as follows: ≤ 1 cm, 1-3 cm, 3-5 cm, 5-10 cm, and ≥ 10 cm. The count of H. lugubris individuals in each growth stage was converted into its percentage with respect to the entire population, which yielded the finding that stages 1 through 5 accounted for 32.8%, 25.3%, 15.9%, 22.5%, and 3.5%, respectively. This suggests that the population of H. lugubris in ASPA No. 171 has a stable reverse J-shaped population structure, with the younger individuals outnumbering mature ones. The mean density of H. lugubris was 17.6/0.25 m², mean canopy cover 13.3%, and the mean dry weight 37.8 g/0.25 m². It began to produce spore in the sizes over 3 cm, and most individuals measuring 5-10 cm were adults with sexually mature apothecia. The spatial distribution of H. lugubris was highly heterogeneous. The major factors influencing its distribution and performance were found to be the period covered by snow, wind direction, moisture, size of the substrate, and canopy cover of Usnea spp. Based on these factors, we constructed a prediction model for estimating the spatial distribution of H. lugubris. Conclusively, the major factors for the spatial distribution of H. lugubris were snow, wind, substrate and the competition with Usnea spp. These results are important for understanding of the distribution in the maritime Antarctic and evolution of H. lugubris that claims a unique life history and ecological niche.