• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3601-3604
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• 2016

Background: The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemoattractant for natural killer cells, monocytes, and memory T lymphocytes. However, any role in the genesis of salivary gland tumors (SGT) is unknown. To assess the diagnostic relevance of chemokines in SGT, MCP-1 levels in the serum of patients were investigated in association with tumor progression and clinical aggressiveness. Materials and Methods: Using an ELISA kit, we assessed and compared the circulating levels of MCP-1 in blood serum of 70 SGT patients with 44 healthy control samples. Results: The results of this study showed that the concentration of MCP-1 was significantly lower in patients with benign ($463.8{\pm}158.5pg/ml$, P=0.033) and malignant ($454.8{\pm}190.4pg/ml$, P=0.007) SGT than in healthy subjects ($645.7{\pm}338.9$). No significant difference in mean serum levels of MCP-1 was observed between the benign and malignant group (p=0.9). While MCP-1 levels were lower in patients with an advanced clinical stage, advanced tumor size, higher tumor grade, or lymph node involvement, but the mean MCP-1 level between groups showed no statistically significant difference (p>0.05). Conclusions: MCP-1 levels in the serum of patients with SGT were decreased, indicating that this might a good marker for discriminating patients with SGT from healthy people. However, no clear-cut relationship was detected between MCP-1 levels and clinicopathologic factors, and MCP-1 is not a good marker for evaluating tumor dissemination.

• 대한한방내과학회지
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• 제15권2호
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• pp.174-196
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• 1994

In order to investigate the effect of Samulbyulgapchoengpitang(SB) and one herb added(SBA) on anti-tumor and immune response, the author performed this experimental study, Tumor weight(TW), mean survival days(MSD) and body weight(BW) in vivo, natural killer cell activity(NKCA). rosette forming cells(RFC), phagoctic activity in recticuloendomethrial system(PA), delayed type hypersensitivity(DTH), hemoagglutinin titer(HA) and hemolysine(HL) in vitro were measured in mice. 1. MSD was prolonged in both of treated groups(SB and SBA) as compared with control group. 2. TW was decreased in both of treated groups with statistical significance as compared with control group. 3. BW was increased in both of treated groups and just only in SB with statistical significance as compared with control group. 4. DTH was increased in both of treated groups with statistical significance as compared with control group. 5. HA was increased in both of treated groups with statistical significance as compared with control group. 6. HL was increased in both of treated groups with statistical significance as compared with control group. 7. RFC was increased in both of treated groups and just only in SB with statistical significance as compared with control group. 8. NKCA was increased in both of treated groups with statistical significance as compared with control group. 9. PA was increased in both of treated groups with statistical significance as compared with control group. According to the above experimental results, it is suggested that SB and SBA will have anti-tumor substance and enhance the effect of immune response. But we have to consider the longtime prescription of SBA because there have been no experiments in its side effect or accumulation in body.

• Genomics & Informatics
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• 제14권3호
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• Journal of Animal Science and Technology
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• 제64권6호
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• pp.1117-1131
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• 2022

Previous studies reported that Bifidobacterium animalis ssp. lactis HY8002 (HY8002) improved intestinal integrity and had immunomodulatory effects. Lactobacillus plantarum HY7717 (HY7717) was screened in vitro from among 21 other lactic acid bacteria (LAB) and demonstrated nitric oxide (NO) production. The aims of this study were to investigate the individual and combined ex vivo and in vivo effects of LAB strains HY8002 and HY7717 at immunostimulating mice that have been challenged with an immunosuppressant drug. The combination of HY8002 and HY7717 increased the secretion of cytokines such as interferon (IFN)-γ, interleukin (IL)-12, and tumor necrosis factor (TNF)-α in splenocytes. In a cyclophosphamide (CTX)-induced immunosuppression model, administration of the foregoing LAB combination improved the splenic and hematological indices, activated natural killer (NK) cells, and up-regulated plasma immunoglobulins and cytokines. Moreover, this combination treatment increased Toll-like receptor 2 (TLR2) expression. The ability of the combination treatment to upregulate IFN-γ and TNF-α in the splenocytes was inhibited by anti-TLR2 antibody. Hence, the immune responses stimulated by the combination of HY8002 and HY7717 are associated with TLR2 activation. The preceding findings suggest that the combination of the HY8002 and HY7717 LAB strains could prove to be a beneficial and efficacious immunostimulant probiotic supplement. The combination of the two probiotic strains will be applied on the dairy foods including yogurt and cheese.

• Natural Product Sciences
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• 제28권3호
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• pp.121-129
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• 2022

Despite considerable efforts, cancer remains an aggressive killer worldwide. Chemotherapeutic drugs that are currently in use lead to destructive side effects and have not succeeded in fulfilling expectations. For centuries, medicinal plants are used for treating various diseases and are also known to have anticancer activity. The main aim of this research was to evaluate antiproliferative activity of saffron, clove, fenugreek, and green tea on Vero and MDA-MB-231 cell lines and to subsequently analyze the effect of these extracts on IRAK-4, TAK1, IKK-alpha, IKK-beta, NF-Kappa B, IRF3, IRF7 genes in Toll Like Receptors (TLRs) pathway. Antiproliferative assay was done by Neutral Red Dye uptake assay. Methanolic extract of green tea was found to be most effective against both cell lines as IC₅₀ was achieved at least concentration of the extract. For molecular studies, MDAMB-231 cells were sensitized with methanolic extract of green tea at same IC₅₀, and RT-PCR was performed to determine the relative expression of genes. Expression of IRAK-4, TAK1, IKK-beta, NF-Kappa B, IRF3 genes was down regulated and IRF7 and IKKalpha was upregulated. Green tea has a potential cytotoxic effect on both cell lines which was demonstrated by its effect on the expression of (TLRs) pathway genes.

• Journal of Ginseng Research
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• 제47권2호
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

• 한국약용작물학회지
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• 제13권1호
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• pp.41-47
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• 2005

족제비싸리의 각 부위별 추출물의 정상세포에 대한 독성을 살펴보기 위하여 인간 정장 폐세포인 HEL299를 이용하였으며 각 추출물은 1.0 g/l의 농도에서 최고 22.2%의 세포독성을 나타내었다. 또한 항암활성효과를 살펴보기 위하여 2가지의 암세포를 이용하였는데, A549와 AGS에서 뿌리 추출물의 경우 1.0 g/l의 농도에서 70%정도의 높은 억제활성을 나타내었고, 또한 암세포의 생육활성에 대한 정상 세포의 세포독성의 비로 나타낸 선택적 사멸도는 고농도에서는 모두 1.5이상으로 나타나 모두 암세포에 대한 선택성이 있는 것으로 나타났다. 면역세포의 생육 촉진 실험을 위하적 인간의 B cell과 T cell을 이용하였으며 각 추출물의 농도를 $0.5 g/l로 하여 실험을 실시하였다. 생육도는 T cell의 경우 배양 6일째 수피 추출물이 $7.5{\times}10^4\;cells/ml$의 세포농도를 나타냈으며 B cell의 경우 배양 5일째 $4.5{\times}10^4\; cells/ml$의 농도를 나타내었다. 면역세포를 이용한 cytokine의 분비량 측정실험에서는 뿌리의 추출물이 배양시간에 따른 cytokine의 분비가 가장 높게 나타나는 것을 확인 할 수 있었다. 각 세포의 $TNF-{\alpha}$의 분비량은 6일째 최고의 분비량을 나타내었고 뿌리추출물의 경우 대조구에 비해 $7{\sim}8$배 가량 정도 더 높은 분비량을 나타낸 것으로 확인되었다. IL-6의 경우 5일째까지 감소하다가 6일째부터 증가하는 경향을 나타내었는데 잎과 열매에서 가장 높은 분비량을 나타내었다. 또한 족제비싸리 추출물을 첨가한 배지에 의한 B cell과 T cell의 면역활성 및 cytokine의 분비량에 따른 NK cell의 면역 활성을 측정하였으며 모든 추출물에서 배양 시간에 따라 유의적으로 증가하는 것을 확인하였다. 그 중 족제비싸리의 수피 추출물에서 B cell의 경우 $14.2{\times}10^4\;cells/ml$, T cell의 경우 $14.2{\times}10^4\;cells/ml$으로 가장 높은 생육 활성을 나타내었다.

• Radiation Oncology Journal
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• 제14권3호
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• pp.229-236
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• 1996

목적 : 방사선 치료시 주기적으로 시행하는 말초 혈액 검사에서 백혈구 성분 중 림프구 수의 감소가 관찰되어, 저자는 방사선 치료 전, 후의 백혈구 성분 및 림프구 아형 분석을 시도하여 방사선 치료가 각 성분에 미치는 영향의 정도를 알아보고자 하였다. 대상 및 방법 : 1994년 12월부터 1995년 5월까지 동아대학교병원 치료방사선과에 내원한 환자 중 16명(폐암, 담관암, 식도암 : 2예, 뇌송과체 종양, 위암, 직장암, 악성 흑색종, 안상 배세포종, 방광암, 전립선 육종, 성상세포종, 다형성교모세포종, 다발성 골전이 폐암 : 1예)을 대상으로 하였다. 방사선 치료는 2700 cGy에서 6660 cGy까지 시행하여 정중앙 총 방사선량이 5400 cGy였다. 백혈구 및 감별계산에서 방사선 치료 전과 후의 백혈구 및 림프구, 단핵구, 과립구의 절대값과 백분을을 구하였고 림프구 아형의 분석은 유세포분석기를 이용하여 총 T 세포, 총 8 세포, 조력유발 T 세포, 억제유발 T 세포, 자연살해세포 등의 절대값과 백분유을 구하였다. 방사선 치료 전후의 절대값파 백분율을 비교하였으며 조력유발T세포에 대한 억제유발 T 세포의 비(Helper/Suppressor T cell ratio)의 변화도 분석하였다. 나아가 방사선량에 따른 각 구성비의 변화 정도를 분석하여 총 방사선량과의 상관 관계를 유추하고자하였다. 결과 : 각 환자에서 방사선 치료 전후에 측정한 값의 비교에서, 백혈구와 그 구성 성분인 림프구, 단핵구및 과립구의 수는 단핵구를 제외하고는 방사선 치료 전에 비하여 감소하였으며 특히 림프구 수의 감소는 통계적으로 유의한 차이를 보였다(p<0.05). 림프구 아형인 총 T 세포, 총 B세포, 조력유발 T 세포, 억제유발 T 세포, 자연살해세포 모두 치료전에 비해 감소하였으며(p$\geq$0.05), 조력유발 T 세포에 대한 억제유발 T 세포의 비(Helper/Suppressor T cell ratio)는 방사선 치료 전 1.52에서 치료후 1.11로 감소하였고(p<0.05) 방사선량에 따른 조력유발 T 세포에 대한 억제유발 T 세포의 비의 방사선 치료 전후에 50 Gy 미만군(5명)과 50 Gy 이상군(11명)에서 각각 0.75와 0.71이었다. 결론 : 방사선 치료 후 림프구 수와 조력유발 T 세포에 대한 억제유발 T 세포의 비는 감소하였고 억제유발 T 세포의 백분율은 증가하였다. 이상의 결과로 림프구 아형 중 조력유발 T 세포가 억제유발 T 세포보다 방사선에 보다 민감한 것으로 사료된다. 본 실험에서 방사선량에 따른 림프구 성분의 변화 분석은 대상군 수가 적고 일회 분할 방사선량이나 치료 부위의 넓이, 환자의 체표 면적의 차이에 따른 제한적 요소가 있었으며 향후 보다 많은 대상군에 대한 심도 깊은 분석이 요구된다.

• 약학회지
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• 제48권6호
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• 한국식품과학회지
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• 제54권2호
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• pp.155-162
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• 2022

본 연구는 돈태반 효소 가수분해물의 면역증진 효과를 확인하고자 Cy를 이용한 면역 저하 모델에서 농도별 돈태반 효소 가수분해물을 투여한 실험군의 주간 체중과 조직 중량, 혈중 면역세포(백혈구, 과립구, 림프구, 중간구) 함량, 혈중 cytokine 및 immunoglobulin 함량, 자연살해세포 활성, 비장 조직 분석을 수행하였다. 체중은 대조군과 비교하여 돈태반 효소 가수분해물을 투여한 실험군 중 중농도 투여군(1.03 mg/kg BW, total nitrogen)과 고농도 투여군(2.07 mg/kg BW, total nitrogen)에서 다소 증가하는 경향을 보였고, 조직 중량은 돈태반 효소 가수분해물을 투여한 실험군이 Cy만을 단독 투여한 대조군에 비해 다소 높았으며, 이 중 고농도 투여군은 비장과 흉선 조직 중량 모두에서 대조군보다 유의적으로 높게 조사되었다. 각 실험군별 비장 조직을 이용한 자연살해세포 활성 분석 결과 정상군에 비해 대조군은 유의하게 감소하였으나 돈태반 효소 가수분해물을 고농도로 투여한 실험군과 양성대조군은 대조군에 비해 증가하는 경향을 보여 정상군과 유사한 수준을 보였다. 일반 혈액학적 분석(CBC analysis)에서 돈태반 효소 가수분해물을 투여한 실험군은 대조군에 비해 백혈구와 과립구, 림프구 및 중간구에서 모두 높은 함량을 보이는 것으로 나타났는데, 특히 고농도 투여군은 백혈구의 경우 양성 대조군인 HemoHIM 투여군과 유사한 수준으로, 과립구와 중간구의 경우 양성대조군보다 더 높은 함량을 보이는 것으로 조사되었다. 혈중 cytokine과 immunoglobulin의 함량을 분석한 결과 돈태반효소 가수분해물을 투여한 실험군에서 혈중 TNF-α와 IL-1β, IL-2, IL-12 및 IgG의 함량을 대조군과 비교하여 유의하게 증가시키거나 증가시키는 경향을 보였다. 또한 조직학적 분석에서 비장조직은 대조군에서 관찰되던 백색수질의 붕괴와 적색수질에서의 세포 응축현상은 돈태반 효소 가수분해물을 투여한 실험군에서 점차 호전되는 경향을 보였다. 이러한 결과를 바탕으로 돈태반효소 가수분해물은 Cy로 인한 세포와 조직 손상을 감소시키고 혈중 면역 관련 인자들의 함량을 증가시켜 면역력을 증진시키는데 긍정적인 영향을 미치는 것으로 판단되며, 추후 이를 활용한 건강 기능성 개발 및 의약품 개발에 따른 활용가치가 매우 높을 것으로 생각된다.