• 대한의생명과학회지
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• 제29권3호
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• pp.178-183
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• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• 미생물학회지
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• 제27권4호
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• pp.422-429
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• 1989

Auxotrophic mutant were isolated from wild types by the treatment with NTG as a mutagen, and the conditions of protoplast formation for them were established. The protoplasts of killer yeast Saccharomyces cerevisiae K52 were formed to the level of above 70% when cells grown for 20 hr in PM medium were treated with 200 unit/ml Lyticase 50,000 at $30^{\circ}C$ for 60 min after pretreatment of 50 mM 2-mercaptoethanol in 10mM potassium phosphate buffer (pH 7.5) containing EDTA and 0.6 M sorbitol for 15 min. Also, the protoplast of the recipient S. cerevisiae S 29 were formed to the level of above 85% as it was cultured to the log phase of 24 hr in PM medium under the same conditions. The fusion frequency between the protoplast of killer yeast S. cerevisiae K 52 and the protoplast of recipient S. cerevisiae S 29 was reached to $8.2\times 10^{-6}$ when the hypertonic regeneration medium embeded with the fused protoplasts after mixing the parental protoplasts to 10$^{8}$ cells/ml in SP buffer containing 20 mM $CaCl_{2}$ and 30% PEG 6,000 for 15 min at $30^{\circ}C$ were incubated.

• IMMUNE NETWORK
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• 제12권6호
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• pp.240-246
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• 2012

Natural killer (NK) cells play a pivotal role in early surveillance against virus infection and cellular transformation, and are also implicated in the control of inflammatory response through their effector functions of direct lysis of target cells and cytokine secretion. NK cell activation toward target cell is determined by the net balance of signals transmitted from diverse activating and inhibitory receptors. A distinct feature of NK cell activation is that stimulation of resting NK cells with single activating receptor on its own cannot mount natural cytotoxicity. Instead, specific pairs of co-activation receptors are required to unleash NK cell activation via synergy- dependent mechanism. Because each co-activation receptor uses distinct signaling modules, NK cell synergy relies on the integration of such disparate signals. This explains why the study of the mechanism underlying NK cell synergy is important and necessary. Recent studies revealed that NK cell synergy depends on the integration of complementary signals converged at a critical checkpoint element but not on simple amplification of the individual signaling to overcome intrinsic activation threshold. This review focuses on the signaling events during NK cells activation and recent advances in the study of NK cell synergy.

• 생약학회지
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• 제22권4호
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• pp.233-239
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• 1991

Phellinus linteus was examined for its anticancer activity using an animal model. Water extract of Phellinus linteus was prepared from artificially cultivated mycelia. Neither toxicity nor abnormal changes of hematological parameters were observed in the rat given orally with high doses of drug extract for 15 days. ICR mice were transplanted with Sarcoma-180 tumor cells intraperitoneally and drug extract was daily given to the mice from 1 day after tumer transplantation for 3 weeks. Administration of drug extract significantly prolonged the survival duration of Sarcoma 180-transplanted mice. For the better understanding of the anticancer activity, we have examined the effect of the drug extract administration on various killer cell functions, such as natural killer(NK) cells, cytotoxic T-lymphocytes (CTL) and macrophages which have been known to be main effector cells in immune responses against tumors. The results from the 4 hr $^{51}Cr-release$ assay have shown that the drug extract augments mouse NK cell activity but neither CTL nor macrophages. It is possible, then, that the anticancer activity of the Phellinus linteus may be associated with augmentation of NK cell function in the cancerated hosts.

• 대한의생명과학회지
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• 제28권3호
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• pp.206-210
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• 2022

Calystegia dahurica (Herb.) Choisy is a natural product that has not been studied for efficacy or active ingredients. The purpose of this study is to investigate the activation effect of natural killer cells using a natural extract composition based on Calystegia dahurica (Herb.) Choisy extract (CDCE). We evaluated the activity of natural killer cells in natural products using PBMCs from healthy participants. All natural products were extracted with 50% ethanol. Based on the results of the cell viability assay, PBMCs of healthy participants were treated with extracts at various concentrations. Then, analysis was performed using flow cytometry to measure the cd107a surface expression of natural killer cells. As a result, treatment with a single extract of PBMCs increased the expression of cd107a in a concentration-dependent. Furthermore, it was confirmed that the treatment of the extract composition showed the highest expression of cd107a. In conclusion, it is expected that the extract composition containing CDCE according to this study can be used for prevention or treatment of cancer cells, tumor cells, and immune diseases.

• 약학회지
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• 제54권3호
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• pp.192-199
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• 2010

Colorectal cancer is one of the most common alimentary malignancies. In this study, the antitumor activity of activated human natural killer (NK) cells against human colorectal cancer was evaluated in vivo. Human NK cells are the key contributors of innate immune response and the effective functions of these cells are enhanced by cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured with interleukin-2 (IL-2)-containing medium for 14 days and resulted in enriched NK cell population. The resulting populations of the cells comprised 7% $CD3^+CD4^+$ cells, 25% $CD3^+CD8^+$ cells, 13% $CD3^-CD8^+$ cells, 4% $CD3^+$CD16/$CD56^+$ cells, 39% $CD3^+$CD16/$CD56^-$ cells, and 52% $CD3^-$CD16/$CD56^+$ cells. Tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), IL-2, IL-4, and IL-5 transcripts of the activated NK cells were confirmed by RT-PCR. In addition, activated NK cells at doses of 2.5, 5 and 10 million cells per mouse inhibited 10%, 34% and 47% of SW620-induced tumor growth in nude mouse xenograft assays, respectively. This study suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for colorectal cancer patients.

• 약학회지
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• 제55권3호
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• pp.267-272
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• 2011

Human NK cells, identified 30 years ago based on their ability to spontaneously kill tumor cells, constitute a subset of lymphocytes, which play an important role in the first line of immune defense and the effective function of these cells are enhanced by cytokines. Lung carcinoma has been one of the most commonly diagonosed cancer as well as the leading cause of cancer death in male. Here we provide the evidence that human natural killer cells has inhibitory effects on tumor growth of human lung cancer cell NCI-H460 (non-small cell lung cancer). Enriched NK cell population was obtained by 2 weeks cultivation in interleukin-2(IL-2)-containing medium. The resulting population comprised 26% CD3$^+$ cells, 9% CD3$^+$CD4$^+$ cells, 16% CD3$^+$CD8$^+$ cells, 76% CD56$^+$ cells, 6% CD3$^+$CD56$^+$ cells and 70% CD3$^-$CD56$^+$ cells. Activated NK cells at doese of 2.5, 5, and 10 million cells per mouse inhibited 2%, 12% and 45% of NCI-H460-induced tumor growth in nude mouse xenograft assays, repectively. This result suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for lung cancer patients.

• Parasites, Hosts and Diseases
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• 제30권2호
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• pp.101-112
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• 1992

원발성 아메바성 수막뇌염을 일으키는 병원성이 강한 자유생환 아에바인 Acanthnmogbn culbertsoni이 영양형을 CSH/HeJ 마우스에 $1{\times}I0^4과{\;}1{\times}10^5$마리씩을 각각 감염시킨 후 12시 간, 1일, 2일, 5일, 10일 째에 감염 마우스를 희생하여 비장 세포의 부유액을 만들어 YAC-1 표적세포에 대한 세포독성을 $^{51}Cr$ 방출 검사법으로 측정하였고 단세포 독성 검사법으로 표적세포 결합능, 환성 자연살세포, 더 나아가 최대 자연살세포 살해능 및 최대 재순환능을 측정하였다. 감염 마우스의 사망률은 아메바 영양형 $1{\times}10^4$마리를 감염시켰을 때 34%이었으며 $1{\times}10^5$을 감염시켰을 때는 65%이었다. 또한 접종 후 20일까지 사망한 마우스의 평균 생존 기간은 각각 $16.40{\pm}3.50,{\;}13.20{\pm}4.09$ 일이었다. 자연살세포의 세포독성은 두 실험군 모두에서 아메바 접종 후 12시간 째에 대조군에 비하여 유의하게 증가하기 시작하여 접종 후 1일 째 가장 높았다. 2일 후에는 대조군과 비슷한 수준을 보였고 전종 후 10일 째에는 대조군에 비해 저하되었으며, 두 실험군 간에 차이는 발견할 수 없었다. 아메바 영양형 $1{\times}10^5$마리를 감염시킨 군에서 표적세포 결합능은 접종 후 12시간, 1일째에 유의하게 증가하였고 환성 연살세포도 비슷한 경향으로 증가하였으나 재순환능은 감염 겹과 시간 별로 대조군과 비교하여 차이를 발견할 수 없었다. 이상의 결과를 종합하면 A. culbertsoni 감염에 의해 비장세포의 자연살세포 독성이 증가하였는데, 이는 자연살세포의 표적세포 결합능과 활성 자연살세포수의 증가와 유의한 상관관계가 있고(p<0.05) 자연살세포의 재순환능과는 무관한 것으로 나타났다.

• Archives of Pharmacal Research
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• 제15권1호
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• pp.20-29
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• 1992

Effects of squalene on cellular and non-specific immune responses and antitumor activity in mice were investigated. Cellular and non-specific immunological assay parameters adopted in the present study were delayed-type hypersensitivity reaction and resette forming cells (RFC) for cellular immunity, activities of natural killer (NK) cells and phagocyte for non-specific immunity. Squalene resulted in marked increases of cellular and non-specific immune functions and enhancement of host resistance to tumor challenge in dose-dependent manner.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.167-167
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• 2008