• Journal of Gastric Cancer
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• v.24 no.1
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• pp.29-56
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• 2024

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

• International Journal of Oral Biology
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• v.38 no.4
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• pp.141-147
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• 2013

It has been established that berberine has strong antimicrobial effects. Little is known however regarding the antimicrobial activity of berberine against endodontic pathogenic bacteria or its cytotoxicity in human oral tissue cells. The antibacterial properties of berberine were tested against 5 strains of Enterococcus faecalis and type strains of Aggregatibacter actinomycetemcomitans, Prevotella nigrescens, Prevotella intermedia, and Tannerella forsythia, which are involved in endodontic infections. Antimicrobial activity was evaluated through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) measurements. The viability of normal human gingival fibroblast (NHGF) cells after exposure to berberine was measured using a methyl thiazolyl tetrazolium (MTT) assay. The data showed that berberine has antimicrobial effects against A. actinomycetemcomitans with an MIC and MBC of $12.5{\mu}g/ml$ and $25{\mu}g/ml$, respectively. In the cytotoxicity studies, cell viability was maintained at 66.1% following exposure to $31.3{\mu}g/ml$ berberine. Overall, these findings suggest that berberine has antimicrobial activity against the tested bacteria. Nevertheless, lower concentrations in combination with other reagents will need to be tested before these in vitro results can be translated to clinical use.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.2
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• pp.105-110
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• 2017

Prolonged exposure to solar ultraviolet A (UVA) radiation has been known to cause premature skin aging (photo-aging). UVA radiation generates ROS thereby induce degenerative changes of skin such as degradation of dermal collagen, elastic fibers. Matrix metalloproteinases (MMPs), the proteolytic enzymes have been implicated as a major player in the development of UVA-induced photo-aging. Many studies have been conducted to block the harmful effects of UV radiation on the skin. Recently, we are interested in the availability of fermented red ginseng (FRG) as natural matrix metalloproteinases inhibitors (MMPIs). The efficacy difference between red ginseng and FRG has been compared. Both RG and FRG have no cytotoxic effects below the concentration of $300{\mu}g/ml$. Human dermal fibroblasts (HDFs) were pretreated with FRG or RG for 24h, followed by irradiation of UVA. Then, we measured the intracellular ROS production and the expression of MMP, $IL-1{\beta}$ at the mRNA level. We also examined the intracellular localization of $NF-{\kappa}B$ and MMP-9 on the FRG or RG treated and UVA-irradiated HDFs. FRG decreased the intracellular ROS production elicited by UVA. In addition, FRG decreased the mRNA expression of MMP-3, MMP-9, and $IL-1{\beta}$ more efficiently than RG. Furthermore, FRG suppressed the nuclear localization of $NF-{\kappa}B$, and the expression of MMP-9. Taken together, our results suggest that FRG is promising agents to prevent UVA-induced photo-aging by suppressing MMP expression and inflammation.

• The Journal of Korean Academy of Prosthodontics
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• v.43 no.3
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• pp.393-408
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• 2005

Statement of problem. In the process of bone formation, titanium (Ti) surface roughness is an important factor modulating osteoblastic function. Purpose. This study was carried out to determine the effect of different Ti surface on biologic responses of a human osteoblast-like cell line (MG63). Materials and methods. MG63 cells were cultured on S (smooth), SLA (sandblasted largegrit & acid etching), HA (hydroxyapatite) Ti. The morphology and attachment of the cells were examined by SEM. The cDNAs prepared from total RNAs of MG63 were hybridized to a human cDNA microarray (1,152 elements). Results. The appearances of the surfaces observed with SEM were different in the three types of dental substrates. The surface of SLA and HA were shown to be rougher than S. MG63 cells cultured on SLA and HA were cell-matrix interaction. In the expression of genes involved in osseointegration, upregulated genes were bone morphogenetic protein, Villin, Integrin, Insulin-like growth factors in different surfaces. Downregulated genes were fibroblast growth factor receptor 4, Bcl 2-related protein, collagen, CD4 in different surfaces. Conclusion. The attachment and expression of key osteogenic regulatory genes were enhanced by surface roughness of the dental materials.

• Korean Journal of Medicinal Crop Science
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• v.17 no.4
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• pp.257-265
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• 2009

Phosphatidylcholine was used to encapsulate aqueous extracts of Centella asiatica, and its biological activity was compared with another aqueous extracts. Nanoparticle of C. asiatica was made by encapsulation to w/o type spherical liposome which of aqueous extracts seized with oil phase as 78.2 nm average diameter. Cytotoxicity of the nanoparticle was measured on human skin fibroblast cells, CCD-986sk, and showed lower cytotoxicity on 1.0 mg/$m{\ell}$ of highest concentration as 28% than that of another extracts. The nanoparticle showed the highest promotion of human B and T cell growth up to 138% and 135%, respectively, compared to the control. and the NK cell growth was promoted up to 8% higher than the control in proportion to secretion of IL-6 and TNF-$\alpha$ from immune cell growth. Also nanoparticle showed highest inhibition activity of hyaluronidase on 1.0 mg/$m{\ell}$ of highest concentration as 60.5%. It seems that because of enhanced biological application of aqueous extracts on cell through nano-encapsulation process.

• Biomedical Science Letters
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• v.12 no.2
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• pp.119-125
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• 2006

In relation to the tissue engineering, the cellular responses to the morphology of the scaffold surface are interesting topics. Human ligament fibroblasts (HLFs) were cultured on the micrpatterned silicone substrates subjected to cyclic stretch to simulate ligament motion. Groove and ridge width of silicone substrates was 10/50, 20/50, 20/10, and 20/20 ${\mu}m$ (groove/ridge ${\mu}m$) with a depth of $3{\mu}m$. Strain was applied over two days for 4 hours per day with a frequency of 0.5 Hz with the magnitudes of 4 or 8%. The purpose of this study was to evaluate ligament fibroblast alignment and cellular responses in relation to the pattern of microgrooved surface and stretching magnitude. Ligament fibroblasts in the microgrooved surface were elongated and aligned parallel to the microgrooves under no stretch. Uniaxial cyclic stretch induced cellular activities and their orientation rise in cellular response and the cells showed alignment and elongation perpendicular to the direction of the stretch. Biochemical analyses showed that the best cellular response was found on the $20/50{\mu}m$ under 8% stretch. The surface morphology and mechanical stretching were found to contribute to increase of proliferation, collagen production.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.229-233
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• 2010

Pluripotency and self-renewal capacity of human embryonic stem cells (hESCs) are retained by hESCs related genes as OCT4, SOX2 and NANOG. These genes are shown high expression level in diverse cancer cells and have potential role in the carcinogenesis. On the contrary to this, several genes which are up-regulated in the differentiated hESCs are involved to suppress the carcinogenesis or proliferation of cells. We discovered several genes in immortalized lung fibroblast (WI-38 VA13) by suppression subtractive hybridization. Among them, we focused chromosome 6 open reading frame 62 (C6orf62) which is uncharacterized, mapped to 6p22.3 and generated to Hepatitis B virus X-transactivated proteins (HBVx-transactivated proteins, XTP). Aim of this study was to characterize C6orf62 through analyzing of expression pattern in various cell lines. Expression of C6orf62 was significantly upregulated in diverse normal cell lines than cancer cell lines. And C6orf62 was up-regulated in differentiated hESCs (endothelial cells, neural cells) compared to those of undifferentiated hESCs. Also, C6orf62 in WI-38 cells was highly up-regulated during G1/S transition of the cell cycle. Taken together, C6orf62 is shown expression pattern similar to differentiated hESCs-associated genes which down-regulated in cancer cells. Therefore, we assume that C6orf62 may participate to suppress the proliferation and to induce differentiation through regulating the cell cycle.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.272-278
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• 2006

Purpose: This study is designed to evaluate biocompatibility of three types of absorbable collagen GBR membrane in vitro. Material and Method: The human PDL fibroblasts culture was obtained through typical way and the cells used in the experiment was forth passage. The membranes examined were Experimental group A, B, C. All the 3-experimental groups were made of bovine pericardium and the membranes were excised into 5$\times$5mm respectively. The samples of the membranes were fixed on the 24-well plate with the double-sided adhesive tape. Then, 2ml of cell suspension which included $2{\times}10^4$cells was inoculated into the 24-well plate, and the cells were cultured for 1 week. Cellular viability and the alkaline phosphatase activity were measured with ELISA. The membranes in the culture were processed to examine with SEM. Results: The survival rate was highest in control and Experimental group A is the next, group B and group C in order of the value. The values are analyzed for statistical difference using Wilcoxon test. All the values of experimental groups are significantly lower than those of control, and the vaules among the experimental groups significantly differ from each other. Alkaline phosphatase level was identical order with the viable cell rate. SEM examination revealed that the PDL fibroblasts adherent on culture dish (control) and group A were spindle-shaped, but on group B and C, the cells were round-shaped without processes.

• Applied Microscopy
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• v.3 no.1
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• pp.29-38
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• 1973

Introduction. The human cutaneous scars manifest themselves many ways in different types according to the factors such as the age, sex, race of the patient as well as the location,. kind and heal ing process of the wound. Among the scars it is quiet difficult to verify the clinical course of the hypertrophic or keloidal scars from the true keloids. However, clinical observations indicate that stress, either mechanical or in the forms of chronic infections, can induce a functional change in the fibroblasts causing an excessive production of collagenous matrix. In this study, we preliminary attempt to justify any difference of the cellular structure between keloids and hypertrophic scars by using electron microscope. Material and Methods. A total of 23 cases: 2 scars, 2 hypertrophic scars and 19 keloids are examined. Immediately, the biopsy tissue was fixed in 10% neutral formalin and 4% glutaraldehyde solution in phosphate buffer for 4 hours, post fixed in 1 % osmium tetraoxide for two hours, dehydrated with graded alcohol, and embedded in Epon 812. Thick sections were stained with hematoxylin eosin, periodic acid-Schiff(PAS) and Van Gieson stain. Thin sections were cut and uranyle acetate, lead citratestain and examined with the electron microscope. Result. The morphologic features of keloid showed thick, homogenously eosinophilic bands of collagen and numberous large active fibroblasts. The hypertrophic scar and soft scar are more cellular than keloid and composed thinner collagenous fiber. For this paper in the etiology of keloids can not as be defined, but and interesting keloidal tissue fibroblast showed irregular nucleus with irregular shape dense bodies and fibril materials contained in to the cytoplasm.

• International Journal of Oral Biology
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• v.33 no.2
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• pp.51-58
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• 2008

A mutation of UNCL, an inner nuclear membrane RNAbinding protein, has been found to eliminate mechanotransduction in Drosophila. UNCL is expressed in human periodontal tissue including in periodontal ligament (PDL) fibroblasts. However, it is unclear how a mechanical stimulus is translated into cellular responses in PDL fibroblasts. The aim of this study was to evaluate the effect of UNCl on mechanical stress related genes in PDL fibroblasts in response to mechanical stress. The mRNA of TGF-$\beta$, COX-2, and MMP-2 was up-regulated after UNCL inactivation in PDL fibroblasts under the compression force. Under the tensile force, inactivation of UNCL decreased the expression of Biglycan, RANKL, MMP-2, and TIMP-2 mRNAs while it increased the expression of TIMP-1. p38-MAPK was expressed in PDL fibroblasts under compression forces whereas phospho-ERK1/2, p65-NFkB, and c-fos were expressed under tension forces. The expression and phosphorylation of the mechanical stress related genes, kinases, and transcription factors were changed according to the types of stress. Furthermore, most of them were regulated by the inactivation of UNCL. This suggests that UNCL is involved in the regulation of mechanical stress related genes through the signaling pathway in PDL fibroblasts.