• 대한한방종양학회지
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• 제3권1호
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• pp.129-147
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• 1997

현재 서양의학에서 활용되고 있는 항암 요법으로는 외과처치(外科處置), 화학요법(化學療法), 방사선요법(放射線療法) 및 면역요법(免疫療法) 등(等)이 있으며, 그 중에서도 항암제(抗癌劑)에 의한 화학요법과 방사선요법이 가장 많이 응용되고 있다. 그런데 이들은 암세포(癌細胞)뿐만 아니라 정상세포(正常細胞)까지도 살상(殺傷)함으로써 종양세포(腫瘍細胞)를 억제하는 동시에 골수조혈기(骨髓造血器), 소화계통(消化系統) 및 면역기능(免疫機能)을 포함하는 인체의 정상적인 기능을 손상시키는 문제점으로 그 사용에 제한을 받고 있다. 따라서, 본 연구는 삼용부정탕(蔘茸扶正湯)의 항암요법으로 손상된 조직의 회복 및 조혈촉진 효과를 규명하기 위해 생쥐를 대상으로 하여 실험하였다. 그 결과, 생쥐 비장세포에 대한 증식효과(增殖效果), 조혈촉진인자(造血促進因子)의 분필능(分泌能), 방사선에 대한 임파구의 방어효과(防禦效果), 방사선에 대한 조혈세포 방어효과(防禦效果), 방사선(9Gy)을 조사받은 생쥐의 생존율(生存率) 등에서 유의성 있는 결과를 얻어내어 아래와 같이 보고하는 바이다.

• Clinical and Experimental Reproductive Medicine
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• 제28권2호
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• pp.161-167
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• 2001

Objective: Granulocyte-macrophage colony stimulating factors known to be secreted in murine and human reproductive tract. The development of human, bovine and murine embryos could be promoted by addition of GM-CSF in culture medium. However, the pregnancy and implantation rate of embryos cultured in GM-CSF have not been evaluated. The aim of this study was to assess the effect of GM-CSF in embryo development, pregnancy and implantation rate. Methods: A total of 191 IVF cycles were divided into control and GM-CSF supplement group (control=96, GM-CSF=95). The embryos were cultured for three day with or without 2 ng/ml of recombinant human GM-CSF. The quality of embryo, developmental velocity, pregnancy and implantation rates were compared. Results: There was no difference in age, number of gonadotropin ampules used, number of oocytes and fertilization. The number of ICSI cycle was higher in GM-CSF group. In GM-CSF group, G-1 grade embryos were the highest in proportion (56.4%), while G-2 grade embryos were highest (44.3%) in control group. The developmental velocity of embryos were not different between GM-CSF and control group. The pregnancy and implantation rates were significantly higher in GM-CSF group than control (47.4% vs. 33.3%, 17.0% vs. 11.1% respectively). Conclusion: By adding GM-CSF in culture medium, the quality of embryo, pregnancy and implantation rate could be improved.

• Journal of Ginseng Research
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• 제37권4호
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• pp.389-400
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• 2013

Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation ($30mJ/cm^2$), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.

• 대한수의학회지
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• 제43권4호
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• pp.607-613
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• 2003

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.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.836-843
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• 2004

Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

• Journal of Yeungnam Medical Science
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• 제28권1호
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• pp.60-69
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• 2011

Due to its efficacy and tolerability, low dose oral methotrexate (MTX) therapy has been widely used for treatment of rheumatoid arthritis (RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease (CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240 mg) and 4 years (cumulative dose 1,320 mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells (RECs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included REC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

• Molecules and Cells
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• 제40권10호
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• pp.706-713
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• 2017

Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptorassociated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 (AP-1). Activated NF-${\kappa}B$ induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces $Ca^{2+}$ oscillation via activated phospholipase $C{\gamma}2$ ($PLC{\gamma}2$) together with c-Fos/AP-1, wherein $Ca^{2+}$ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.

• 한국임상약학회지
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• 제25권2호
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• pp.80-93
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• 2015

Objective: Pegfilgrastim is recently introduced that is long acting G-CSF for prophylaxis of febrile neutropenia. Treatment of non-Hodgikin's lymphoma (NHL) with R-CHOP is classified with relative high risk of febrile neutropenia. The study evaluated the prophylactic effect of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-CHOP of patient in NHL. And the risk factors associated with the incidence of FN and related events were evaluated. Methods: This retrospective study reviews the Electronic Medical Record of 68 NHL patients who received R-CHOP chemotherapy in single center between September 2013 and August 2014. These patients were classified who receive prophylaxis pegfilgrastim or no prophylaxis. Results: Sixty eight patients received R-CHOP with NHL. In 144 cycles of patients receiving pegfilgrastim, compared with no prophylaxis 178 cycles, had a lower incidence of febrile neutropenia (5.5% vs. 23.6%, p = 0.001), grade 3 or grade 4 neutropenia (14.4% vs. 89.8%, p < 0.001) and neutropenia related events (p < 0.05). The risk of febrile neutropenia after prophylaxis was significantly associated with age ${\geq}65$ (OR: 5.87, 95% CI 1.07-32.27, p = 0.042), $IPI{\geq}3$ (OR: 7.2, 95% CI 1.31-39.6, p = 0.023), S.alb < 3.5 g/dL (OR: 31.01, 95% CI 6.32-152.17, p < 0.0001). In multiple logistic regression analysis, lower baseline serum albumin (OR: 21.1, 95% CI 3.8-116.98, p = 0.001) was significantly associated with occurrence of febrile neutropenia. Conclusion: The study recommends prophylactic pegfilgrastim through risk assessment of febrile neutropenia in patients with non-Hodgikin's lymphoma receiving R-CHOP.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3909-3919
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• 2013

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

• 대한수의학회지
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• 제52권4호
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• pp.231-238
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• 2012

The expression profiles of inflammatory cytokines viz. interleukins (IL)-6, IL-8, IL-12, granulocyte macrophage-colony stimulating factor, interferon-${\gamma}$ and tumor necrosis factor-${\alpha}$ in response to subclinical mastitis in indigenous cattle breed Kankrej (n = 6), Gir (Bos indicus) (n = 12) and crossbred (Bos taurus${\times}$Bos indicus) (n = 7) were investigated using quantitative real time PCR. Significant correlation (p < 0.05) was observed between total bacterial load and somatic cell count (SCC) in all three breeds of cattle. All the cytokines were observed to be up-regulated compared to cows with healthy quarters, however, level of their expression varied among three breeds of cattle. In Kankrej most cytokines were found to be transcribed to higher levels than in other two breeds; the milk had higher load of bacteria but not so high SCC, implying that Kankrej has a higher inherent resistance against mastitis. The results of present study indicated that mammary glands of crossbred cattle are more sensitive to bacterial infection than indigenous breed of cattle as they elicit immune response at lower bacterial load and result into higher SCC. Research on identification of factors responsible for differentially expressed cytokines profiles and use of cytokines as immunomodulatory tools can pave way for formulating control strategies against bovine mastitis.