• 한양메디칼리뷰
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• 제33권1호
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• pp.59-64
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• 2013

Cancer remains the leading cause of death worldwide despite intense efforts in developing innovative treatments. Current approaches in cancer therapy are mainly directed to a selective targeting of cancer cells to avoid potential side effects associated with conventional therapy. In this respect, Natural killer (NK) cells have gained growing attention and are now being considered as promising therapeutic tools for cancer therapy owing to their intrinsic ability to rapidly recognize and kill cancer cells, while sparing normal healthy cells. NK cells play a key role in the first line of defense against transformed and virus-infected cells. NK cells sense their target through a whole array of receptors, both activating and inhibitory. Functional outcome of NK cell against target cells is determined by the balance of signals transmitted from diverse activating and inhibiting receptors. Despite significant progress made in the role of NK cells attack as a pivotal sentinel in tumor surveillance, the molecular has been that regulate NK cell responses remain unclear, which restricts the use of NK cells as a therapeutic measure. Accordingly, current efforts for NK cell-based cancer therapy have largely relied on the strategies that are based on the manipulation of inhibitory receptor function. However, if we better understand the mechanisms governing NK cell activation, including those mediated by diverse activating receptors, this knowledge can be applied to the development of optimal design for cancer immunotherapy by targeting NK cells.

• Clinical and Experimental Reproductive Medicine
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• 제36권3호
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• pp.199-207
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• 2009

목 적: 말초혈액 자연살해세포가 증가된 반복유산 환자군과 증가되지 않은 반복유산 환자군에서 다음 번 유산 시탈락막의 자연살해세포의 발현양상을 관찰하여 말초혈액 자연살해세포와 상관관계가 있는지 보고자 하였다. 연구방법: 말초혈액 자연살해세포가 15% 이상 증가된 반복유산 환자군 14명을 실험군으로, 15% 이하인 군 12명을 대조군으로 하여 연구를 진행하였다. 이 환자들에게서 다음 번 유산 시 착상부위를 포함한 자궁 탈락막 세포를 확인하여 면역조직화학염색을 통해 $CD56^+$와 $CD16^+$ 자연살해세포의 수를 세어 실험군과 대조군을 비교하였다. 결 과: 실험군과 대조군은 탈락막 내 $CD56^+$ 자연살해세포의 수 간에 통계적으로 유의한 차이 ($170.1{\pm}132.1$ vs. $68.3{\pm}66.1$, p=0.02)를 보였으나 둘 간의 상관관계 (r=0.229, p=0.261)는 없었다. 또한 두 군간에 $CD16^+$ 자연살해세포는 통계적으로 유의한 차이 ($25.70{\pm}11.72$ vs. $31.17{\pm}22.67$)를 보이지 않았다. 결 론: 본 연구는 말초혈액 $CD56^+$ 자연살해세포가 증가된 반복유산 환자군에서 말초혈액 자연살해세포가 증가되지 않은 군에 비하여 탈락막의 $CD56^+$ 자연살해세포가 증가되어 있음을 알 수 있었다. 이는 탈락막 자연살해세포가 반복유산의 면역학적 기전에서 중요한 역할을 할 것이라는 가능성을 제시해 주는 연구 결과이며 또한 말초혈액 자연살해세포의 측정이 반복유산 환자에서 다음 번 유산을 예측할 수 있는 유용한 지표임을 알 수 있다.

• IMMUNE NETWORK
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• 제7권3호
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• pp.133-140
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• 2007

Background: It is well established that cross talk between natural killer (NK) cells and myeloid dendritic cells (DC) leads to NK cell activation and DC maturation. In the present study, we investigated whether type 1-polarized DC (DC1) matured in the presence of IFN-${\gamma}$ and type 2-polarized DC (DC2) matured in the presence of PGE2 can differentially activate NK cells. Methods: In order to generate DC, plastic adherent monocytes were cultured in RPMI 1640 containing GM-CSF and IL-4. At day 6, maturation was induced by culturing the cells for 2 days with cytokines or PGE2 in the presence or absence of LPS. Each population of DC was cocultured with NK cells for 24 h. The antigen expression on DC was analyzed by flow cytometry and cytokine production in culture supernatant was measured by ELISA or a bioassay for TNF-${\alpha}$ determination. NK cell-mediated lysis was determined using a standard 4h chromium release assay. Results: DC2, unlike DC1, had weak, if any, ability to induce NK cell activation as measured by IFN-${\gamma}$ production and cytolytic activity. DC2 were weakly stimulated by activated NK cells compared to DC1. In addition, IFN-${\gamma}$-primed mature DC appeared to be most resistant to active NK cell-mediated lysis even at a high NK cell/DC ratio. On the other hand, PGE2-primed DC were less resistant to feedback regulation by NK cells than IFN-${\gamma}$-primed mature DC. Finally, we showed that the differential effect of two types of DC population on NK cell activity is not due to differences in their ability to form conjugates with NK cells. Conclusion: These results suggest that different combinations of inflammatory mediators differentially affect the effector function of DC and, as a result, the function of NK cells, eventually leading to distinct levels of activation in adaptive immunity.

• Restorative Dentistry and Endodontics
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• 제29권3호
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• pp.239-248
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• 2004

The purpose of this study was to investigate the influence of NK1 receptor antagonists on the pulpal blood flow (PBF) when applied iontophoretically through the dentinal cavity of the teeth in order to understand whether iontophoretically applied NK1 receptor antagonists can control the pulpal inflammation. Eleven cats were anesthetized with alpha-chloralose and urethane, and substance P (SP) was administered to the dental pulp through the catheterized lingual artery in doses that caused PBF change without the influence of systemic blood pressure. NK1 receptor antagonists were applied iontophoretically to the prepared dentinal cavity of ipsilateral canine teeth of the drug administration, and PBF was monitored. Data were analyzed statistically with paired t-test. PBF increase after iontophoretic application of the NK1 receptor antagonists followed by the intra-arterial administration of SP was significantly less than PBF increase after iontophoretic application of the 0.9% saline followed by the intra-arterial administration of SP as a control (p < 0.05). Iontophoretic application of the NK1 receptor antagonists (0.2~3.4 mM) following the intra-arterial administration of SP resulted in less increase of PBF than the iontophoretic application of the 0.9% saline following the intra-arterial administration of SP as a control (p < 0.05). Therefore. the results of the present study provide evidences that the iontophoretic application is an effective method to deliver drugs to the dental pulp. and that iontophoretically applied NK1 receptor antagonists block SP-induced vasodilation effectively. The above results show the possibility that the iontophoretical application of NK1 receptor antagonists can control the neurogenic inflammation in the dental pulp.

• 대한두경부종양학회지
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• 제33권1호
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• pp.35-38
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• 2017

The extranodal nasal NK/T-cell lymphoma was formerly known as lethal midline granuloma due to its most common clinical pattern like a destructive midline facial tumor. It often spread to other extranodal sites, such as skin, soft tissue, testis, upper respiratory tract, and gastrointestinal tract etc. For this reason, the term of extranodal NK/T-cell lymphoma, nasal type is preferred. Its disease entity may have a prominent admixture of inflammatory cells and necrotic tissues, further causing difficulty in diagnosis. A 44-year-old man was visited to our clinic with complaints of dysphagia and odynophagia during six months. He underwent three times punch biopsies and then, two times incisional biopsies. Finally, He was diagnosed as extranodal NK/T-cell lymphoma, nasal type involving oropharynx and supraglottis. We report an extremely rare case of extranodal NK/T-cell lymphoma, nasal type occurred in oropharynx and supraglottis with a brief review of literature.

• 한국축산식품학회지
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• 제42권6호
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• pp.928-941
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• 2022

This study aimed to analyze the microbiological composition and sensory characterization of fermented sausage using strains isolated from Kimchi (GK1, Pediococcus pentosaceus SMFM2016-GK1; NK3, P. pentosaceus SMFM2016-NK3), Doenjang (D1, Debaryomyces hansenii SMFM2021-D1), and spontaneously fermented sausage (S8, D. hansenii SMFM2021-S8; S6, Penicillium nalgiovense SMFM2021-S6). The control was commercial starter culture. Nine treatments were applied [GD (GK1+D1), GS (GK1+S8), GDS (GK1+D1+S8), ND (NK3+D1), NS (NK3+S8), NDS (NK3+D1+S8), GND (GK1+NK3+D1), GNS (GK1+NK3+S8), and GNDS (GK1+NK3+D1+S8)] by mixing lactic acid bacteria and yeast, and S6 was sprayed. The microbial composition of fermented sausage was analyzed [aerobic bacteria (AC), Lactobacillus spp. (LABC), Staphylococcus spp. (STPC), and yeast and mold (YMC)], and pH and electronic nose and tongue measurements were taken. The AC, LABC, STPC, and YMC values of the control and treatment groups tended to increase during fermentation (p>0.05). The STPC values of the GD, GS, ND, and GDS groups were similar to that of the control on day 3. The pH of the control on day 3 was significantly lower than that of the GD, ND, and GND groups (p<0.05). Higher levels of 4-methylpentanol, 2-furanmethanol, and propyl nonanoate, which provide a "fermented" flavor, were detected in the GD group compared to in the control and other treatment groups. GD and ND groups showed higher umami values than the control and other treatment groups. Therefore, it is expected that GD can be valuable as a starter culture unique to Korea when manufacturing fermented sausage.

• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1369-1374
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• 2019

We isolated Lactobacillus mucosae NK41 and Bifidobacterium longum NK46 from human feces, which induced BDNF expression in corticosterone-stimulated SH-SY5Y cells, and examined their anti-depressive effects in mice. NK41, NK46, and their (1:1) mixture significantly mitigated immobilization stress (IS)-induced anxiety-like/depressive behaviors, hippocampal $NF-{\kappa}B$ activation, BDNF expression, $Iba1^+$ cell population, and blood corticosterone, $TNF-{\alpha}$, IL-6, and lipopolysaccharide levels. Furthermore, they inhibited colitis marker $NF-{\kappa}B$ activation, and $TNF-{\alpha}$ expression in mice with IS-induced anxiety/depression. They additionally suppressed gut Proteobacteria and Bacteroidetes populations and bacterial lipopolysaccharide production. These findings suggest that NK41 and NK46 may alleviate anxiety/depression and colitis by suppressing gut dysbiosis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1661-1675
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• 2016

Objectives: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. Materials and Methods: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. Results: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, P<0.001), acute phase (85.1% vs 79.6%, P<0.001), and delayed phase (71.4% vs 58.2%, P<0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, P<0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, P<0.001; occurrence of vomiting: 22.6% vs 38.9%, P<0.001; usage of rescue drugs: 23.5% vs 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. Conclusions: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

• Journal of Acupuncture Research
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• 제33권2호
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• pp.1-9
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• 2016

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

• BMB Reports
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• 제52권9호
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• pp.554-559
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• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.