• 대한의용생체공학회:의공학회지
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• 제28권5호
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• pp.676-683
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• 2007

A non-invasive respiratory gated radiotherapy system like those based on external anatomic motion gives better comfortableness to patients than invasive system on treatment. However, higher correlation between the external and internal anatomic motion is required to increase the effectiveness of non-invasive respiratory gated radiotherapy. Both of invasive and non-invasive methods need to track the internal anatomy with the higher precision and rapid response. Especially, the non-invasive method has more difficulty to track the target position successively because of using only image processing. So we developed the system to track the motion for a non-invasive respiratory gated system to accurately find the dynamic position of internal structures such as the diaphragm and tumor. The respiratory organ motion tracking apparatus consists of an image capture board, a fluoroscopy system and a processing computer. After the image board grabs the motion of internal anatomy through the fluoroscopy system, the computer acquires the organ motion tracking data by image processing without any additional physical markers. The patients breathe freely without any forced breath control and coaching, when this experiment was performed. The developed pattern-recognition software could extract the target motion signal in real-time from the acquired fluoroscopic images. The range of mean deviations between the real and acquired target positions was measured for some sample structures in an anatomical model phantom. The mean and max deviation between the real and acquired positions were less than 1mm and 2mm respectively with the standardized movement using a moving stage and an anatomical model phantom. Under the real human body, the mean and maximum distance of the peak to trough was measured 23.5mm and 55.1mm respectively for 13 patients' diaphragm motion. The acquired respiration profile showed that human expiration period was longer than the inspiration period. The above results could be applied to respiratory-gated radiotherapy.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.165-171
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• 2007

Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.761-766
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• 2012

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.618-624
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• 2017

Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with $IC_{50}$ of approximately $2.0{\mu}M$. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.

• 한국콘텐츠학회논문지
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• 제11권5호
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• pp.32-40
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• 2011

저속촬영이 가능한 현미경을 통해 얻어진 세포동영상에서 세포활동의 추적 및 분석은 종양의 전이, 바이러스의 침입, 상처회복, 세포분열과 같은 복잡한 생물학적 과정을 이해하는데 있어 매우 중요한 역할을 담당한다. 세포추적의 자동화를 위해서는 각 프레임에서의 세포검출, 전후 프레임 내 세포들의 상관관계 조사, 새로운 세포의 인식 및 세포분열의 확인 등과 같은 일련의 작업들이 수행되어야 한다. 본 논문에서는 이를 위한 효과적인 자동 세포 추적 알고리즘을 제시한다. 첫 번째 프레임에서는 세포영역의 특성 분석을 통해 얻어진 특징벡터를 이용하여 각 세포의 마커 영역을 추출하고, 여기에 워터쉐드 알고리즘을 적용함으로써 세포 분할을 수행한다. 연속된 프레임들에서는 이전 프레임의 분할결과를 이용하여 현재 프레임에서의 분할 과정이 수행된다. 그리고 각 세포의 기하학적 특성과 밝기 특성의 결합 비용함수를 사용하여 전후 프레임 간 세포의 올바른 상관관계를 조사함으로써 세포 추적의 정확도를 개선한다. 실험에서 세포영상 분석을 위한 소프트웨어 패키지인 CellProfiler와의 비교/분석을 통해 제안 알고리즘의 효율성을 입증하였다.

• 약학회지
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• 제47권5호
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• 대한수의학회지
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• 제61권2호
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• pp.14.1-14.7
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• 2021

Biosilica is a silica-based substance derived from the cell walls (frustules) of diatoms. Recently, research into biosilica's biological functions is underway, but little has been reported on the effects of biosilica on immune cells. In this study, we investigated the effect of ionized biosilica water (iBW) on dendritic cells (DCs), which play crucial roles as antigen (Ag)-presenting cells. Treatment with iBW increased the expression of immune response-related markers, closely connected to the maturation of DCs, and the production of tumor necrosis factor-alpha. In addition, iBW-treated DCs (iBW-DCs) had a lower uptake of fluorescein isothiocyanate-dextran than that of control DCs. Mixed leukocyte response analysis used for measuring the Ag-presenting capability of DCs, showed iBW-DCs had a higher capability than that of control DCs. Interestingly, DCs treated with lipopolysaccharide (LPS) and iBW had a lower level of Ag-presenting capability than that of LPS-treated DCs. Taken together, the results indicate that iBW alone can mature DCs, but it decreases the Ag-presenting capability of DCs in the presence of LPS, a representative agent of inflammation. This study may provide valuable information regarding the effect of iBW on immune cells. Further research is needed to investigate how iBW induces the observed biphasic immunomodulatory activity.

• 치위생과학회지
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• 제23권4호
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• pp.264-270
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• 2023

Background: Resin-based dental materials release residual monomers or other substances from incomplete polymerization into the oral cavity, thereby causing adverse biological effects on oral tissue. 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP), an acidic monomer containing dihydrogen phosphate and methacrylate groups, is the most commonly used component of resin-based dental materials, such as restorative composite resins, dentin adhesives, and resin cements. Although previous studies have reported the cytotoxicity and biocompatibility in various cultured cells, the effects of resin monomers on cellular aging have not been reported to date. Therefore, this study aimed to investigate the effects of the resin monomer 10-MDP on cellular senescence and inflamm-aging in vitro. Methods: After stimulation with 10-MDP, MC3T3-E1 osteoblast-like cells were examined for cell viability by WST-8 assay and reactive oxygen species (ROS) production by flow cytometry. The protein and mRNA levels of molecular markers of aging were determined by western blotting and RT-PCR analysis, respectively. Results: Treatment with 0.05 to 1 mM 10-MDP for 24 hours reduced the survival of MC3T3-E1 cells in a concentration-dependent manner. The intracellular ROS levels in the 10-MDP-treated experimental group were significantly higher than those in the control group. 10-MDP at a concentration of 0.1 mM increased p53, p16, and p21 protein levels. Additionally, an aging pattern was observed with blue staining due to intracellular senescence-associated beta-galactosidase activity. Treatment with 10-MDP increased the levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8, however their expression was decreased by mitogen-activated-protein-kinase (MAPK) inhibitors. Conclusion: Taken together, these results suggest that the exposure of osteoblast-like cells to the dental resin monomer 10-MDP, increases the level of cellular senescence and the inflammatory response is mediated by the MAPK pathway.

• BMB Reports
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• 제57권2호
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• pp.98-103
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• 2024

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

• Journal of Applied Biological Chemistry
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• 제58권3호
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• pp.219-226
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• 2015

본 연구에서는 레몬 잎 메탄올 추출물(MLL)의 인간 유방암 줄기 세포인 MCF-7-SC에 대한 항암 활성을 조사하였다. MLL이 MCF-7-SC에서 apoptosis를 유도하였으며, 이를 apoptotic body의 형성, sub-G1 phase 및 annexin V-positive 세포와 Bax/Bcl-2 ratio의 증가, caspase-9과 caspase-3의 활성화 및 PARP의 절 단을 통하여 확인하였다. 동시에 MCF-7-SC에서 MLL은 acidic vesicular organelles의 형성, LC3-II의 축적 증가, Akt/mTOR/p70S6K의 활성 억제 등을 통하여 autophagy를 유도하였다. Epithelial-mesenchymal transition (EMT)는 세포가 전이 상태를 획득하기 위한 중요한 과정이며, 이 기작은 암세포가 전이되는 것을 억제함에 있어서 중요한 표적이 된다. 낮은 농도에서의 MLL은 epithelial 마커 단백질인 E-cadherin이 증가와 mesenchymal 마커 단백질인 Snail과 Slug의 발현 감소를 통해 EMT 과정을 저해함으로써 MCF-7-SC에서 항전이 활성을 나타내었다. 본 연구에서는 레몬 잎 메탄올 추출물이 농도 의존적으로 유방암 줄기세포에 대해 세포 독성과 항전이 활성을 나타내고 있으며, 따라서 레몬잎은 항암 소재로서의 개발 가능성이 높은 식물이라고 사료된다.