치료중인 유방암 환자의 신체적 증상과 자연살해세포 활성도의 관계

채영란 대한기초간호자연과학회 2002 Journal of korean biological nursing science Vol.4 No.2

The purpose of this study was to identify the relationship of symptorn discress and natural killer cell cytotoxicity in breast cancer patients who had been radiation therapy and/or chemotherapy after surgery. Symptom distress measured by modified Lee's(1994) physical symptom questionnaire. For measuring the natural killer cell cytotoxic activity, 8ml to 10ml blood was collected from the subjects. Mononuclear cell was isolated by centrifuge of the blood and cultured by putting Cr^(51) , and reacted with target cell, K562 cell. Amount of Cr^(51) was measured, and %lysis was calculated. The results were as follows. 1) Symptom distress score was 42.18, which is moderate symptom distress. 2) Natural killer cell cytotoxic activities were 42.18%lysis(effector : target cell ratio=100 : 1) and 28.05%lysis(effector : target cell ratio=50 : 1). 3) Correlation coefficients of symptom distress and natural killer cell cytotoxic activity were -.134~-.461. Though significant correlation was not found between total score of symptom distress and natural killer cell cytotoxic activity, 3('pain' 'feel hot on radiation site' and 'difficulty in breathing') of 19 symptom distress items and natural killer cell cytotoxic activity showed significant negative correlation(p<.05). These findings suggest that 1) breast cancer patients who had been radiation therapy and/or chemotherapy after surgery have moderate symptom distress and decreased natural killer cell cytotoxic activity. 2) The symptom distress was not related to natural killer cell cytotoxic activity.

Mitomycin-C, Cisplatin, Vinblastine이 마우스 자연살해세포 활성에 미치는 영향

강헌중,김광혁,류현열,박건영 대한암예방학회 2000 Journal of cancer prevention Vol.5 No.3

운동 프로그램이 유방암 환자의 자연살해세포 활성에 미치는 효과

채영란,최명애,김미정 대한기초간호자연과학회 2002 Journal of korean biological nursing science Vol.4 No.2

The purpose of this study was to determine the effect of exercise program on natural killer cell cytotoxic activity(NKCA) in breast cancer patients who had been radiation therapy after surgery. The subjects in the experimental group consisted of 11 breast cancer patients, while the subjects in the control group consisted of 15. Subjects in the experimental group participated in exercise program for 8 weeks. Exercise program consisted of shoulder stretching, arm weight training and treadmill walking exercise. They started to exercise on treadmill for 20 minutes per day, 3 times a week 40% of maximum heart rate, and increased intensity and duration of exercise so that they were running 30 minutes/day at 60% of maximum heart rate from the 3rd week to the 8th week. Natural killer cell cytotoxic activity were determined before and after tht: exercise program. For measuring the natural killer cell cytotoxic activity, 8ml to 10ml blood was collected from the subjects. Mononuclear cell was isolated by centrifuge of the blood and cultured by putting Cr^(51) , and reacted with target cell, K562 cell. Baseline demographic and medical data were compared between groups with the Fisher's exact test and Mann-Whitney U test. For effects of the exercise program, repeated measures ANOVA was used. The result was as follows ; Natural killer cell cytotoxic activity(NKCA) in experimental group comparing with control group significantly increased after the exercise program in case of effector cell : target cell ratio is 100 : 1(p<0.05). The above result suggest that the exercise program for breast cancer patients undergoing radiation therapy after breast surgery may increase the natural killer cell cytotoxic activity.

Anticancer Drugs at Low Concentrations Upregulate the Activity of Natural Killer Cell

권혁진,정명국,최고은 대한의생명과학회 2023 Biomedical Science Letters Vol.29 No.3

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 nonkilling (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.

Impact of Smoking on Human Natural Killer Cell Activity: A Large Cohort Study

Yoon Suk Jung,Jung Ho Park,Dong Il Park,손정일,Jae Myun Lee,Tae Il Kim 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.1

Some studies have reported a decrease in the natural killer (NK) cell activity in smokers. However, large-scale data on the relationship between NK cell activity and smoking are unavailable. A cross-sectional study was performed on 12,249 asymptomatic examinees who underwent an NK cell activity test, between January 2016 and May 2017. The test quantitated the amount of interferon-γ secreted into the plasma by NK cells, using a patented stimulatory cytokine. The mean age of the study population was 39.1 years, and the proportions of “never”, “former”, and “current” smokers were 65.5%, 20.9%, and 13.6%, respectively. Current smokers (1,422 pg/mL) had a lower median level of NK cell activity than never smokers (1,504 pg/mL, P = 0.039) and former smokers (1,791 pg/mL, P < 0.001). Among current smokers, NK cell activity decreased with increase in the number of cigarettes smoked among current smokers (median, 1,537, 1,429, and 1,175 pg/mL at <10, 10-19, and ≥ 20 pack-years, respectively; P < 0.001). Additionally, it decreased linearly with increasing quartiles of cotinine levels (median, 1,707, 1,636, 1,348, and 1,292 pg/mL at cotinine levels < 292, 292-879, 880-1,509, and ≥ 1,510 ng/mL, respectively; r = –0.122, P < 0.001). NK cell activity was lower in current smokers. It also decreased with an increase in the number of cigarettes smoked, and it was negatively correlated with cotinine levels among current smokers. Our findings indicate a clear relationship between smoking and decreased NK cell activity. Keywords : Natural killer cell activity, Smoking, Cotinine

Physical Inactivity and Unhealthy Metabolic Status Are Associated with Decreased Natural Killer Cell Activity

정윤숙,박정호,박동일,손정일,이재면,김태일 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.4

Purpose: Several studies have reported relationships among physical activity, healthy metabolic status, and increased naturalkiller (NK) cell activity. However, large-scale data thereon are lacking. Thus, the present study aimed to assess NK cell activity accordingto physical activity and metabolic status. Materials and Methods: A cross-sectional study was performed on 12014 asymptomatic examinees. Using a patented stimulatorycytokine, NK cell activity was quantitated by the amount of interferon-γ secreted into the plasma by NK cells. Physical activity levelswere assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form. Results: The physically inactive group showed lower NK cell activity than the minimally active group (median, 1461 vs. 1592 pg/mL,p<0.001) and health-enhancing physically active group (median, 1461 vs. 1712 pg/mL, p=0.001). Compared to women with abody mass index (BMI) of 18.5−27.5 kg/m2, those with a BMI <18.5 kg/m2 had significantly lower NK cell activity (1356 vs. 1024 g/mL,p<0.001), and those with a BMI ≥27.5 kg/m2 tended to have lower NK cell activity (1356 vs. 1119 g/mL, p=0.070). Subjects withhigh hemoglobin A1c levels and low high-density lipoprotein cholesterol levels, as well as men with high blood pressure andwomen with high triglyceride levels, exhibited lower NK cell activity. Moreover, physical inactivity and metabolic abnormalitieswere independently associated with low NK cell activity, even after adjusting for confounders. Conclusion: Physical inactivity and metabolic abnormalities are associated with reduced NK cell activity. Immune systems maybecome altered depending on physical activity and metabolic status.

大七氣湯이 抗癌, 免疫調節作用 및 apoptosis에 미치는 影響

하지용,정병억,이선구,유병길 대한동의병리학회 2001 동의생리병리학회지 Vol.15 No.1

Daechilgitang, extracted from Sparganium stoloniferum Buch. Ham, Curcuma zedoaria rosc, Aurantii immatri pericarpium, Fraxini cortex, Platycodon grandiflorum (jacg.) DC., Agaslache rugosa(Fisch.et Mey.) kuntze, Trigonella foenum-graecum L., Cyperus rotundus L., Cinnamomum cassia BI, Glycyrrhiza uralensis Fisch., is known to antitumor agent. This study was performed to investigate antitumor, immune response, and apoptotic effects by Daechilgitang in the cancer lines and Balb/c mice. Experimental studies were progressed through the anticancer activities such as, life extention, cell cytotoxicity, natural killer cell activity, productivity of interleukin-2, apoptotic effects. The results were summarized as follows: 1.Median survival time in Daechilgitang-treated group was prolonged to 16%, as compared with control group. 2.On the MTT assay, half-maximal inhibitory concentration(IC50) of Daechilgitang on cell lines, were 532.3㎎/㎖ in sarcoma-180 cell, and 2.8㎎/㎖ in HT-29 cell. 3.Natural killer cell activity in Daechilgitang-treated group was significantly increased in case of 100:1 effect cell/target cell ratio. 4.Production of interleukin-2 in Daechilgitang-treated group was significantly increased. 5.On the studies of Daechilgitang-induced apoptosis, a DNA fragmentation patterns and electron microscopic appearance were evident, however, activity of MAP kinase was not affected. Key word : Daechilgitang, IC50, anti-tumor, immunomodulatory, interleukin-2, natural killer cell activity, apoptosis, DNA fragmentation, MAP kinase activity

Development of NK cell expansion methods using feeder cells from human myelogenous leukemia cell line

Bae, Duk Seong,Lee, Jae Kwon Korean Society of Hematology; Korean Society of Bl 2014 Blood Research Vol.49 No.3

<P><B>Background</B></P><P>Natural killer (NK) cells constantly survey surrounding tissues and remove newly generated cancer cells, independent of cancer antigen recognition. Although there have been a number of attempts to apply NK cells for cancer therapy, clinical application has been somewhat limited because of the difficulty in preparing a sufficient number of NK cells. Therefore, <I>ex vivo</I> NK cell expansion is one of the important steps for developing NK cell therapeutics.</P><P><B>Methods</B></P><P>CD3<SUP>+</SUP> depleted lymphocytes were cocultured with IL-2 and with feeder cells (peripheral blood mononuclear cells [PBMCs], K562, and Jurkat) for 15 days. Expanded NK cells were tested for cytotoxicity against cancer cell lines.</P><P><B>Results</B></P><P>We compared feeder activities of three different cells-PBMC, K562, and Jurkat. K562 expanded NK cells by almost 20 fold and also showed powerful cytotoxic activity against cancer cells. K562-NK cells remarkably expressed the NK cell activation receptors, NKG2D, and DNAM-1. K562-NK cells exhibited more than two-fold production of cytotoxic granules compared with Jurkat-NK cells, producing more perforin and granzyme B than naïve NK cells.</P><P><B>Conclusion</B></P><P>Our findings suggest that K562 are more efficient feeder cells than Jurkat or PBMCs. K562 feeder cells expanded NK cells by almost 20 fold and showed powerful cytotoxic activity against cancer cells. We herein propose an intriguing approach for a design of NK cell expansion.</P>

Natural killer cells as a promising therapeutic target for cancer immunotherapy

Nayoung Kim,Hyeon Ho Lee,Hyo-Jung Lee,Woo Seon Choi,Jinju Lee,Hun Sik Kim 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.7

Natural killer (NK) cells are innate lymphoidcells that provide early protection against cancer developmentvia their selectivity to kill abnormal cells undergoingcellular transformation without the need for prior stimulation. Given the correlation between NK cell dysfunctionand cancer prognosis, restoration of endogenous NK cellsin the tumor microenvironment or adoptive transfer of NKcells with improved function holds great promise in cancertreatment. Furthermore, MHC-unrestricted tumor lysis byNK cells complements the MHC-restricted killing of tumorcells by cytotoxic T cells, thus positioning NK cells as analternative or complementary therapeutic target for cancersthat are refractory to T cell-based therapy. Although previoustherapeutic strategies have focused on the manipulationof NK cell inhibitory receptors, recent advances inour understanding of NK cell activation have providedadditional promising strategies to enhance NK cell reactivityagainst cancer. These approaches include targetingimmunosuppressive mechanisms in the tumor microenvironment,such as immune checkpoint receptors, and furtherenhancing NK cell activation via modulation of intracellularcheckpoint molecules or incorporation of tumor-directedchimeric antigen receptors. Thus, an in-depthunderstanding of NK cell activation will facilitate theoptimal design of therapeutic strategies against refractorycancers, possibly in rational and synergistic combinationwith other therapies.

Development of NK cell expansion methods using feeder cells from human myelogenous leukemia cell line

Duk Seong Bae,이재권 대한혈액학회 2014 Blood Research Vol.49 No.3

Background Natural killer (NK) cells constantly survey surrounding tissues and remove newly generated cancer cells, independent of cancer antigen recognition. Although there have been a number of attempts to apply NK cells for cancer therapy, clinical application has been somewhat limited because of the difficulty in preparing a sufficient number of NK cells. Therefore, ex vivo NK cell expansion is one of the important steps for developing NK cell therapeutics. Methods CD3+ depleted lymphocytes were cocultured with IL-2 and with feeder cells (peripheral blood mononuclear cells [PBMCs], K562, and Jurkat) for 15 days. Expanded NK cells were tested for cytotoxicity against cancer cell lines. Results We compared feeder activities of three different cells−PBMC, K562, and Jurkat. K562 expanded NK cells by almost 20 fold and also showed powerful cytotoxic activity against cancer cells. K562-NK cells remarkably expressed the NK cell activation receptors, NKG2D, and DNAM-1. K562-NK cells exhibited more than two-fold production of cytotoxic granules compared with Jurkat-NK cells, producing more perforin and granzyme B than naïve NK cells. Conclusion Our findings suggest that K562 are more efficient feeder cells than Jurkat or PBMCs. K562 feeder cells expanded NK cells by almost 20 fold and showed powerful cytotoxic activity against cancer cells. We herein propose an intriguing approach for a design of NK cell expansion.