• Journal of Life Science
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• v.21 no.7
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• pp.953-960
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• 2011

Necrosis is characterized by the cell membrane rupture and release of the cellular contents, including high-mobility group box 1 protein (HMGB1), into the extracellular microenvironment. HMGB1 acts as a transcriptional regulator in nuclei, but exerts a pro-inflammatory and tumor-promoting cytokine activity when released into the extracellular space. Its overexpression is associated with tumor progression and chemoresistance. Thus, HMGB1 acts as a clinically important molecule in tumor biology. In this study, we examined whether HMGB1 affects cell death induced by anti-cancer drugs. Here we show that HMGB1 prevented cisplatin (alkylating agent)-induced apoptosis and switched the cell fate to necrosis in MCF-7, MDA-MB231, and MDA-MB361 cells. Similar apoptosis-to-necrosis switch effects of HMGB1 were observed in cells treated with 4-HC, another alkylating agent. In contrast, HMGB1 did not exert any significant effects on docetaxel (DOC)-induced apoptosis in MCF-7 cells. We also show that cisplatin-induced apoptosis was switched to necrosis in MCF-7 multicellular tumor spheroids (MTS) that were cultured for 8 days and had necrotic cores, but DOC-induced apoptosis was prevented without the apoptosis-to-necrosis switch. Finally, the levels of RAGE, a receptor of HMGB1, were increased with extended culture of MTS. These findings demonstrate that HMGB1 switches alkylating agent-induced apoptosis to necrosis, suggesting that the strategy to prevent necrosis occurring as an undesirable action of alkylating agent-based chemotherapy should be delineated to improve the efficacy of chemotherapy for cancer.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.88-95
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• 2007

Purpose: The purpose of this study was to compare the proapoptotic effects of matrix metal-loproteinase inhibitor (MMPI) and doxorubicin on wild-type p53 osteosarcoma cell line, socalled U2OS cell line. Materials and Methods: U2OS cells were treated with MMP inhibitor III (MMPI III) and doxorubicin, either respectively or simultaneously. In cells treated with doxorubicin, Fas-neutralizing antibody so called ZB4 was additionally treated to examine whether the doxorubicin played a role through the Fas/FasL pathway. Cells were analysed regarding to apoptosis and cell death by flow cytometry. Results: U2OS cells incubated with doxorubicin showed significant amount of cell death in dose-dependent manner. However, those incubated with MMPI III mostly remained viable state. In addition, there is no relationship between two drugs. Cells treated with doxorubicin and ZB4 at the same time did not show down regulation of apoptosis through inhibition of Fas/FasL pathway. Conclusion: It is important to re-examine MMP inhibitor's effect on other osteosarcoma cell line with wild-type p14 as well as wild-type p53 to evaluate its proapoptotic effect.

• Applied Microscopy
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• v.37 no.4
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• pp.239-248
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• 2007

Alteration of temperature is one of cancer therapies. In general, severe hyperthermia(around $43^{\circ}C$) and hypothermia(around $18^{\circ}C$) trigger apoptosis through mitochondria, though the specific mechanism is still unknown. CC-t6 and GB-d1 cell lines, which were originally derived from human cholangiocarcinoma and gall bladder cancer, were established from a metastatic lymph node. To investigate the mechanism of metastatic cancer cell response to thermal stresses, hyperthermia($37^{\circ}C{\rightarrow}43^{\circ}C$) and hypothermia($37^{\circ}C{\rightarrow}17.4^{\circ}C$) were designed. Thermal stresses did not induce apoptosis but necrotic cell death. Any alterations of caspase-3, -9, cytochrome c, Bax, and Bcl-2 were not found in both hyperthermia and hypothermia exposed fells using western blot analysis. In the transmission electron microscopy, typical necrotic, but not apoptotic, changes were observed. These results suggest that temperature changes induce cell death through necrotic pathway in metastatic cancer in vitro, and it can be one of effective anticancer methods.

• Journal of Digital Convergence
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• v.16 no.2
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• pp.19-26
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• 2018

We proposed a numerical calculation of the proportion of necrotic cells in pulmonary segmentation, pulmonary vessel segmentation lung disease site for diagnosis of lung disease from chest CT images. The first step is to separate the lungs and bronchi by applying a three-dimensional labeling technique from a chest CT image and a three-dimensional region growing method. The second step is to divide the pulmonary vessels by applying the rate of change using the first order polynomial regression, perform noise reduction, and divide the final pulmonary vessels. The third step is to find a disease prediction factor in a two-step image and calculate the proportion of necrotic cells.

• Journal of fish pathology
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• v.4 no.2
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• pp.79-85
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• 1991

In Feb., 1990 an epizootic disease to masu salmon fry, Oncorhynchus masou cultured at the hatchery of rainbow trout in Samchok, Kwangwon-do have broken out and induced high mortality over 70%. Externally, the diseased fish showed dark discoloration, abdominal distension with ascites, slight exophthalmus and fecal casts. Internally, the gill and the liver of diseased fish were edematous and pale, and the stomach of moribund fish contained the milkish fluid. Microscopically there was extensive necrosis of the hematopoietic tissue in kidney and spleen, and scattered necrosis of pancreas, liver and lateral muscle. Especially, the necrosis of lamina propria, muscle layer and tela submucosa in the digestive tract known as the typical signs associated with infectious hematopoietic necrosis virus was seen clearly.

• Journal of radiological science and technology
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• v.28 no.3
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• pp.249-254
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• 2005

This study investigated the structural changes of folliculus ovarii according to the dose of the X-rays when mice were exposed to X-rays from 6MeV LINAC. The minute structural changes of folliculus ovarii were observed through an electron microscope with high magnification. Nuclei and protoplasm of granular cells in growing folliculus ovarii abruptly underwent minute structural changes according to the increase of dose of X-rays. Cell residue, by-product of cell decease, neutrophil and macrophage around follicular antrum were observed. The minute structural changes in granular cells showed typical characteristics of apoptosis: the increase of electronic density due to nuclear condensation, fragmentation of nuclei, and atrophy of protoplasm. Necrosis of cells was identified, but it was not so remarkable. Macrophage scattered with apoptotic bodies.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.332-336
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• 2006

Toxic epidermal necrolysis (TEN) is a rare, acute and life-threatening cutaneous drug reaction. TEN is characterized by the sudden onset of extensive necrosis in the epidermis and frequent mucous membrane involvement. The pathogenesis has not yet been elucidated. In addition, no particular treatment for TEN has been established. We report a case of TEN in a 14-year-old-boy, which might have been caused by steroids with enalapril treatment for membranous nephropathy. He recovered after intravenous immunoglobulin therapy.

• Proceedings of the Korean Society of Fisheries Technology Conference
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• 2000.05a
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• pp.440-441
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• 2000

1990년대에 들면서, 온수 양어장에서 버나바이러스(Birnavirus)성 아가미 질병인 2차새변 벽주세포 괴사증(일명: 아가미 점상출혈증)과는 그 증상에서 차이를 보이는 아가미 질병이 발생되었다. 새변의 울혈과 괴사 병변을 주로 나타내는 본 질병은 경우에 따라 가슴지느러미와 아가미 근접복부에 출혈상을 나타내기도 한다. 병어의 병리조직학적 관찰, 분리 바이러스의 생화학적 또는 전자현미경 관찰 및 감염실험을 통해 아가미 질병의 원인 바이러스로도 H. anguillae가 인정되었으므로 이에 그 연구내용을 보고한다. (중략)

• Korean Journal of Plant Tissue Culture
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• v.25 no.3
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• pp.153-158
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• 1998

The internal structures of Arabidopsis thaliana infected with beet curly top virus (BCTV) were studied by light microscopy. Hyperplasia was observed in the inflorescence stems of Arabidopsis thaliana ecotype Sei-O at 2 weeks after BCTV-Logan inoculation and callus was induced on symptomatic tissues at 4 weeks after virus inoculation. The infection processes were revealed as follows: hyperplasia of phloem tissue, necrosis of hyperplastic phloems, lacuna formation of necrotic tissues, elongation and enlargement of cortex and epidermal cells surrounding the lacuna formed phloem tissues, induction of cell division in the enlarged cortex and epidermal cells, and induction of callus tissue. Callus formation on Arabidopsis was caused by the virus infection, and virus inclusion body was observed in both phloem and callus tissue by azure-A staining.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.479-484
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• 2000

흰쥐에 에탄올을 투여해 간 손상을 유도한 후 굼벵이를 투여해 굼벵이가 혈청과 간의 지진대사에 어떠한 영향을 미치는가를 조사하였다. 혈청지질 중 에탄올에 의해 증가된 triglyceride, 총 cholesterol은 굼벵이를 섭취시킴으로써 이의 수치를 감소시켰으며 HDL-cholesterol은 굼벵이의 섭취로 triglyceride 함량은 감소되었다. GOT와 GPT의 활성은 에탄올 투여시 정상식이에 비해 유의적인 증가를 보인 반면, 굼벵이의 섭취로 유의적인 감소를 나타내었다. (p<0.05). 에탄올 추여군의 간조직 세포는 세포질에 지방소적의 축적으로 세포질의 부분적인 괴사현상이 나타났으며 조면소포체와 mitochondria의 형태적 변형이 관찰되었다. 에탄올과 굼벵이의 병용투여군은 지방소적의 크기 및 양적 감소와 세포질의 괴사현상이 약간 회복 되었으나 조면소포체와 mitochondria의 수적인 증가는 미미하였다.