• Molecules and Cells
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• 제41권8호
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• pp.753-761
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• 2018

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is identified as a signaling adaptor protein that regulates bone metabolism, immunity, and the development of several tissues. Therefore, its functions are closely associated with multiple diseases. TRAF6 is also involved in the regulation of hematopoiesis under steady-state conditions, but the role of TRAF6 in modulating hematopoietic stem and progenitor cells (HSPCs) during the developmental stages remains unknown. Here, we report that the deletion of TRAF6 in hematopoietic lineage cells resulted in the upregulation of HSPCs in the fetal liver at the prenatal period. However, in the early postnatal period, deletion of TRAF6 drastically diminished HSPCs in the bone marrow (BM), with severe defects in BM development and extramedullary hematopoiesis in the spleen being identified. In the analysis of adult HSPCs in a BM reconstitution setting, TRAF6 played no significant role in HSPC homeostasis, albeit it affected the development of T cells. Taken together, our results suggest that the role of TRAF6 in regulating HSPCs is altered in a spatial and temporal manner during the developmental course of mice.

• 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.

• 대한의생명과학회지
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• 제28권4호
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• Journal of Ginseng Research
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• 제48권3호
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• pp.266-275
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• 2024

Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

• Tuberculosis and Respiratory Diseases
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• 제48권2호
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• pp.149-154
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• 2000

배 경: 결핵에 대한 인체의 면역반응의 근간을 이루는 것은 대식세포가 결핵균을 탐식하여 사멸시키는 것이다. 이 과정에는 Interferon-gamma(IFN-$\gamma$)와 Tumor necrosis factor-alpha(TNF-$\alpha$) 가 중요한 역할을 한다. 저자들은 phytohemagglutinin(PHA) 혹은 purified protein derivative(PPD)에 의한 말초혈액 단핵구의 IFN-$\gamma$와 TNF-$\alpha$의 분비능이 폐결핵 환자들에서 치료함에 따라 어떻게 변화하는지를 살펴보고자하였다. 방 법: 폐결핵으로 확진되었고 전형적인 임상상을 보이는 치료시작 전 환자 5명, 치료시작 후 4개월이내의 환자 11명, 치료시작 후 4 개월에서 9개월 사이의 환자 6명 그리고 치료를 종료한 환자 7명을 대상으로 하였다. 환자의 말초혈액 단핵구를 분리하여 PHA와 PPD로 자극한 후 IFN-$\gamma$와 TNF-$\alpha$를 측정하여 서로 비교하였다. 결 과: 각 군간에 PHA와 PPD로 자극한 후 말초혈액 단핵구의 IFN-$\gamma$와 TNF-$\alpha$의 분비능은 차이가 없었다. 결 론: 전형적인 임상상을 보이는 폐결핵환자들에서 그 치료 시점에 따른 IFN-$\gamma$와 TNF-$\alpha$의 분비능의 차이는 없었다.

• 대한한방종양학회지
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• 제3권1호
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• pp.1-27
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• 1997

This study was performed to investigate the effects of Eunwhasagantang and Eunwhasagantangganokyong on the viability of tumor cells in vitro(MTT assay), on antitumor effects after Sarcoma-180 cells transplantation into the peritoneal cavity or left groin, and on decreased immune responses in mice induced by methotrexate. The extracts of its herbal medicines were orally administered for 14 or 21 days. To evaluate the effects of the Eunwhasagantang and Eunwhasagantangganokyong many items such as 50% inhibitory concentration($IC_{50}$), mean survival days, tumor and body weight for antitumor effects, and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity, lymphocyte transformation, productivity of interleukin-2 and phagocytic activity for immune responses were measured in ICR mice. The results were obtained as follows; 1. $IC_{50}$ of Eunwhasagantang treated group was 0.000204mg/ml on SNU-396 and that of Eunwhasagantangganokyong treated group was 0.000103mg／ml on SNU-1, those results indicate that the medicine has high antitumor activity. 2. Mean survival times in Eunwhasagantang and Eunwhasagantangganokyong treated groups were slightly increased with no significance, as compared with the control group. 3. Tumor weight in Eunwhasagantang and Eunwhasagantangganokyong treated group was depressed, as compared with the control group(p<0.01). 4. Body weight in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05). 5. Delayed type hypersensitivity in Eunwhasagantang and Eunwhasagantang-ganokyong treated group was slightly decreased with no significance, as compared with the control group. 6. Hemagglutinin titer in Eunwhasagantang and Eunwhasagantangganokyong treated group was slightly increased with no significance, as compared with the control group. 7. Hemolysin titer only in Eunwhasagantang treated group was significantly increased, as compared with the control group(p<0.01). 8. Rosette forming cells only in Eunwhasagantangganokyong treated group was slightly increased with no significance, as compared with the control group. 9. In the NK cell activity, the ratio of effector cells and target cells of the Eunwhasagantang treated group was significantly increased(p<0.01) in case which the ratio was 100: 1, and that of the Eunwhasagantangganokyong treated group was significantly increased(P<.01, p<0.05) in case which the ratio was 100:1, 50:1, as compared with the control group. 10. Lymphocyte trasnformation in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.01). 11. Interleukin-2 in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05, p<0.01). 12. Phagocytic activity in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05). According to the above results, it could be suggested that Eunwhasagantang and Eunwhasagantangganokyong have prominent antitumor effects, and enhance both cellular and humoral immunity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2447-2451
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• 2015

Background: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. Materials and Methods: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Results: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. Conclusions: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1321-1326
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• 2014

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제41권
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• pp.56.1-56.6
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• 2019

Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

• KSBB Journal
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• 제24권1호
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• pp.80-88
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• 2009

glandular kallikrein에 광범위한 상동성을 가지는 인간 전립성 산성 인산 가수분해 효소는, 전립선암의 대표적인 혈청 biomarkers이다. 수지상세포는 유력한 항원 제시 세포이며, 바이러스, 미생물 병원체 및 종양에 대하여 면역 계통에서 강력한 T 세포 응답을 유도할 수 있다. 따라서, 종양 특이적인 항원으로 감작된 수지상세포를 이용한 면역요법은 anti-tumor 면역 유도를 위한 강력한 방법중의 하나이다. 크레아젠(주)에서 개발된 CTP (세포막 투과성 펩티드) 기술은 세포 내로의 높은 침투 효율성을 가지며 핵산이나 단백질과 같은 생체 고분자 물질을 접합하여 세포내로 수송할 수 있는 기술이다(36). 하지만 활성형의 인간 전립성 산성 인산 가수분해 효소는 세포사멸을 매개할 수 있기 때문에, 본 연구진은 항암 치료용 백신으로의 수지상세포 감작을 위해 비활성형 형태의 다중체 (multimer) 항원을 개발하였다. 본 연구에서, 수지상 세포의 감작과 활성화에 안전하고 효율적인 다중체 형태 (multimeric form)의 세포막 투과성 펩티드가 융합된 인간 전립성 산성 인산 가수분해 효소를 얻기 위한 정제공정을 기법을 개발하였고 젤 여과 크로마토그래피, western blot과 Dynamic Light Scattering을 이용하여 확인하였다. 아울러, 정제된 다중체 형태 (multimeric form)의 세포막 투과성 펩티드가 융합된 인간 전립성 산성 인산 가수분해 효소는 수지상 세포의 감작시 세포질 내로 효과적으로 침투되었다. 결과적으로 세포의 사멸의 부작용이 없이 MHC class I 분자를 통해 수지상세포의 표면으로 효과적으로 제시되었다.