위암에서 Galectin-3 단백질 발현에 관한 연구

주홍구,우희종 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.4

The expression of galectin-3 protein in four different gastric cancer cell lines and lymph node tissues of patients with gastric carcinoma was studied by Western blotting, immundhistochenustry and flow cytometry analysis. Western blot analysis of galectin-3 using anti-galectin-3 , mAb indicated that a 29 kDa protein was expressed in 3 gastric cancer cell lines, AGS, KATO BI , and SNU16, but not in SNU1 which was a non-adherent cell line. Interestingly, SNU16 cells secreted galectin-3 into the culture media. Flow cytometry analysis revealed that NIH3T3, AGS, and KATO III cells expressed the galectin-3 on the cell surface. The level a))' galectin-3 expression was highest in AGS (91.5%), high in KATO M (69.5%), and low in NIH3T3 (55.8%). The gastric cancer cells metastasized into .lymph node tissues were heavily stained whereas normal lymphocytes were not stained. This study suggested that the expression of galectin-3 and the metastasis of gastric cancer cells might be correlated.

Granulocyte-macrophage colony stimulating factor protects dendritic cells from anticancer drug-induced apoptosis

주홍구,Joo, Hong-Gu The Korean Society of Veterinary Science 2003 大韓獸醫學會誌 Vol.43 No.4

Dendritic cells (DCs) play an essential role in a variety of immune reactions involving $CD4^+$ T cells and have been used to enhance tumor-specific immune responses. Immunosuppression in patients with cancer includes the downregulation of function and number of DCs. Although DCs have been studied, the apoptosis of Des induced by anticancer drugs for chemotherapy remains largely uncharacterized. This study demonstrated that GM-CSF protects DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. After 6 - 10 days culture, DCs were characterized by specific surface marker, CD11c and MHC class II. MTT assay revealed that GM-CSF significantly enhanced the viability of DCs treated with 5-FU or mitomycin C. The percentage of dead cells of DCs was determined by cell size using FACScan and GM-CSF was clearly effective. However, GM-CSF did not increase the expression of MHC class II on viable DCs gated, suggesting that GM-CSF may differentially regulate critical factors involved in the function of DCs. For the quantitative analysis of apoptosis, annexin V-FITC staining was performed. 5-FU induced the apoptosis of DCs and GM-CSF significantly protects DCs from 5-FU-induced apoptosis. Taken together, the results in this study that GM-CSF has an anti-apoptosis effect on DCs may provide patients with cancer with clinical benefits to overcome the immunosuppression induced by the decrease of number and functional insufficiency of DCs.

Altered maturation of dendritic cells by taxol, an anticancer drug

주홍구 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.3

Radioprotective activity and stimulatory effects of an acidic polysaccharide of Panax ginseng on bone marrow and immune cells

Hong-Gu Joo(주홍구) 고려인삼학회 2011 고려인삼학회 학술대회 Vol.2011 No.4

항암제 (5-fluorouracil, doxorubicin, vincristine)로 인한 비장세포의 면역억제에 대한 Bordetella bronchiseptica의 보호 효과

이유정,주홍구,Lee, You-Jeong,Joo, Hong-Gu 대한수의학회 2022 大韓獸醫學會誌 Vol.62 No.3

5-Fluorouracil, doxorubicin, and vincristine are chemotherapy agents used to treat various cancers, such as breast cancer and lymphoma for decades, and their effects on cancer have been proven. On the other hand, these anti-cancer drugs cause fatal side effects, including immunosuppression. This study investigated whether sonicated Bordetella bronchiseptica bacterin (B. bronchiseptica) can attenuate the immunosuppression of spleen cells induced by these chemotherapy agents and which subsets of spleen cells were affected. B. bronchiseptica increased the metabolic activity of spleen cells treated with 3 anti-cancer drugs. Cell death analysis using Annexin V/propidium iodide showed that B. bronchiseptica markedly decreased the death of spleen cells. The subsets of spleen cells were analyzed by flow cytometry using a surface marker-specific antibody. B. bronchiseptica increased nitric oxide production in the spleen cells treated with anti-cancer drugs (p < 0.0001). Despite the pharmacological effects of anti-cancer drugs, many patients suffer from the fatal side effects of immunosuppression. This study provides valuable information on how to overcome chemotherapy-induced immunosuppression.

지질다당류로 활성화된 마우스 골수세포에서 구충제 Fenbendazole의 억제 효과

박서로,주홍구,Park, Seo-Ro,Joo, Hong-Gu 대한수의학회 2021 大韓獸醫學會誌 Vol.61 No.3

Fenbendazole (FBZ) is a commonly used anthelmintics in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin V-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. In addition to anthelmintic and anticancer agent, FBZ can play a role as an anti-inflammatory agent.

마우스 림프종세포에 대한 disulfiram/copper의 항암증진효과

정해빈,주홍구,Jung, Haebeen,Joo, Hong-Gu 대한수의학회 2022 大韓獸醫學會誌 Vol.62 No.1

Disulfiram (DSF) is a marketed drug to treat patients with alcohol dependence by inhibiting aldehyde dehydrogenase. Over the last few decades, DSF has been shown to have anticancer effects through different mechanisms. Moreover, this effect can be elevated when used with copper (Cu). Subsequent studies have been conducted on various cancers, but few on lymphoma. This study investigated the anticancer effects of DSF on lymphoma and how this effect changed when treated with Cu. DSF synergistically decreased the metabolic activity of EL4 lymphoma cells when combined with Cu. At 1 µM of DSF alone, the metabolic activity of EL4 cells decreased by 49% compared to the control, whereas it decreased by 87% with a DSF + CuCl₂ treatment. Rhodamine 123 and 2',7'-dichlorofluorescein diacetate staining showed that DSF induced the reduction of the mitochondrial membrane potential and promoted the production of reactive oxygen species. In particular, the combined treatment of DSF + Cu induced cell death based on multiple assays, including annexin V-fluorescein isothiocyanate/propidium iodide staining. Overall, DSF has anticancer effects on lymphoma cells and exhibits synergistic effects when combined with Cu. This study provides some valuable information to broaden the use of DSF in clinics and basic research.

Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production

정한빈,주홍구 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.5

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs’ survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

박서로,주홍구 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.3

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

Bone Marrow Stromal (BMS) Cells Differentiate into Neurons and Transplanted BMS Cells Promote Functional Recovery after Spinal Cord Injury

신태균,주홍구,심기범 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3