• Title/Summary/Keyword: Murine model study

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Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

  • Wang, Wen-Jia;Qin, Si-Hao;Zhang, Ji-Wei;Jiang, Yue-Yao;Zhang, Jin-Nan;Zhao, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9667-9672
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    • 2014
  • Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

The Comparative Study of Fructus Immaturus Ponciri and Fructus Ponciri Effect on Allergic Reaction (알레르기반응에 대한 지실과 지각의 효과 비교 연구)

  • 엄용대;김대한;정종길;신민교;송호준
    • The Journal of Korean Medicine
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    • v.22 no.4
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    • pp.10-21
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    • 2001
  • Objective : To investigate the effect between Fructus Immaturus Ponciri (FIP, the immature fruit of Poncirus trifoliata) and Fructus Ponciri (FP, the ripe fruit of Poncirus trifoliata) on mast cell-mediated immediate-type allergic reactions. Methods : We performed anaphylactic reaction, histamine release, cAMP, $TNF-{\alpha}$, IgE. Results : The aqueous extract of FIP dose-dependently inhibited systemic and local allergic reaction was induced by compound 48/80 or anti-dinitrophenyl (DNP) IgE in a murine model. FIP also significantly inhibited mast cell-dependent ear swelling response induced by topical application of compound 48/80. When mice were orally pretreated with FIP, the plasma histamine levels were reduced in a dose-dependent manner. FIP dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMCs) was activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMCs, when FIP was added, increased compared with that of a normal or control. In addition, FIP had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-a ($TNF-{\alpha}$) production from the RPMCs and IgE produced by lipopolysaccharide-stimulated murine whole spleen cells or U266B1 as human IgE-bearing B cells. However, FP showed the lower inhibition rate than those of FIP in above all allergic reactions. Conclusion : These data have important implications for our understanding of the clinical effects of FIP and FP on allergic diseases, and FIP is more effective than FP on the allergic reaction.

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Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a Component of Polysiphonia morrowii, In Vivo and In Vitro

  • Kang, Na-Jin;Han, Sang-Chul;Kang, Hyun-Jae;Ko, Geum;Yoon, Weon-Jong;Kang, Hee-Kyoung;Yoo, Eun-Sook
    • Toxicological Research
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    • v.33 no.4
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    • pp.325-332
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    • 2017
  • 3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

Anti-melanogenic effects of Hordeum vulgare L. barely sprout extract in murine B16F10 melanoma cells

  • Choi, Jeong-Hwa;Jung, Jong-Gi;Kim, Jung-Eun;Bang, Mi-Ae
    • Journal of Nutrition and Health
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    • v.52 no.2
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    • pp.168-175
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    • 2019
  • Purpose: Barely sprout is a well-known oriental herbal medicine with a wide range of health benefits. Recent studies have provided scientific evidence of its therapeutic effects with expanded application. This study investigated anti-melanogenic effect of barley sprout water extract (BSE) in murine melanocyte B16F10. Methods: Various concentrations (0, 50, 125, and $250{\mu}g/mL$) of BSE and arbutin (150 ppm) were applied to B16F10 stimulated with or without alpha-melanocyte stimulating hormone (100 nM) for 72 hours. The whitening potency of BSE was determined altered cellular melanin contents. Activity and expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were also assayed. Results: Experimental results revealed that treatment with BSE reduced cellular melanin production by approximately 40% compared to the control. Molecular findings supported that suppressed activity and expression of tyrosinase and MITF proteins by BSE were associated with declined cellular melanogenesis. Furthermore, anti-melanogenic effect of BSE ($250{\mu}g/mL$) was similar to that of arbutin, a commonly used whitening agent. Lastly, polyphenols including p-coumaric, ferulic, and vanillic acids were identified in BSE using HPLC analyses. They might be potential active ingredients showing such melanogenesis-reducing effect. Conclusion: BSE was evident to possess favorable anti-melanogenic potency in an in vitro model. As a natural food sourced material, BSE could be an effective depigmentation agent with potential application in pharmaceutical and cosmetic industries.

Protective Role of the Toll-Like Receptor 5 Agonist KMRC011 against Murine Colitis Induced by Citrobacter rodentium and Dextran Sulfate Sodium

  • Jun-Young Kim;Sun-Min Seo;Han-Woong Kim;Woo-Jong Lee;Yang-Kyu Choi
    • Journal of Microbiology and Biotechnology
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    • v.33 no.1
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    • pp.35-42
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    • 2023
  • This study aimed to identify the therapeutic ability of a novel toll-like receptor (TLR) 5 agonist, KMRC011, on ulcerative colitis induced by Citrobacter rodentium and dextran sulfate sodium in a C57BL/6N mouse model. Ulcerative colitis was induced in the mice by the oral administration of 1% dextran sulfate sodium in sterile drinking water for seven days ad libitum, followed by C. rodentium infection on the seventh day by intra-gastric administration (DSS-CT group). KMRC011 was administered intramuscularly at both 24 h and 15 min before (Treatment 1 group), and at both 15 min and 24 h after (Treatment 2 group) the C. rodentium infection. The length of the large intestine and histopathological counts were significantly greater and mucosal thickness was significantly thinner in the Treatment 1 group compared to the DSS-CT and Treatment 2 groups. Il-6 and Il-10 mRNA expression levels were upregulated, while Ifn-γ and Tnf-α mRNA expression levels were significantly downregulated in the Treatment 1 group, compared to the DSS-CT group. NF-κB p65 expression level was elevated due to ulcerative colitis in the DSS-CT group, but was significantly downregulated in the Treatment 1 group. Overall, KMRC011 showed protective effects against murine colitis by inhibiting NF-κB signaling.

Effect of Bifidobacterium Cell Fractions on IL-6 Production in RAW 264.7 Macrophage Cells

  • Lee, Byung-Hee;Ji, Geun-Eog
    • Journal of Microbiology and Biotechnology
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    • v.15 no.4
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    • pp.740-744
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    • 2005
  • Bifidobacterium has been previously shown to potentiate immune function, which was mediated through the stimulation of cytokine production by macrophage. This study was performed to further characterize the effective component of Bifidobacterium by measuring the level of interleukin (IL)-6 cytokine using the RAW 264.7 murine cell line as a macrophage model. RAW 264.7 cells were cultured for 24 h in the presence of whole cells (WCs), cell walls (CWs), and cell-free extracts (CFEs) from various strains of Bifidobacterium and other lactic acid bacteria at various concentrations. The most effective component was different depending on the strains and the concentrations used. When tested with each cell fraction from Bifidobacterium sp. BGN4, heat treatment of the cell fractions lowered the production of IL-6. Synergistic effect was obtained, especially when CWs and CFEs were combined. Sonicated WCs stimulated IL-6 production more than intact WCs. The in vitro approaches employed here should be useful in further characterization of the effects of Bifidobacterium on gastrointestinal and systemic immunity.

Synthesis and Immunosuppressive Activity of Novel Succinylacetone Analogues

  • Kim, Taek-Hyeon;Oh, Dong-Ryun;Na, Hee-Sam;Lee, Hyun-Chul
    • Archives of Pharmacal Research
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    • v.26 no.3
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    • pp.192-196
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    • 2003
  • This study describes the synthesis of novel enol esters (3) and triketones (4) as analogues of succinylacetone (SA) (Ed- this abbreviation is introduced here based on your use of it in the body of the paper) and the evaluation on the mouse allogeneic mixed lymphocyte reaction (MLR) and the murine model of antigen-induced paw edema formation for immunosuppressive activity. Enol esters (3a-f) were about 2-4 fold more potent than SA in in vitro activity.

Effects of Ascaris suum Extract and Sulfamethoxazole on Allergic Airway Inflammation

  • Cho, Eun-Sang;Park, Bae-Keun;Son, Hwa-Young
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.466-471
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    • 2011
  • Allergic asthma is complex inflammatory airway disorder caused by genetic and environmental factors. Sulfamethoxazole, a sulfonamide, is the cause of drug rash with eosinophilia and systemic symptoms syndrome. Parasites infection also related with eosinophilia and allergic diseases. In the present study, we investigated the modulating effects of parasitic derivative and sulfamethoxazole (SMX) on allergic airway inflammation in the ovalbumin (OVA)-induced murine asthma model. Histopathological changes, cytokine secretion, and total and allergen-specific IgE were investigated. BALB/c mice were treated with Ascaris suum extract or SMX for 4 weeks before sensitized and challenged to ovalbumin. Pre-treatment of Ascaris suum extract decreased allergic inflammation in lung tissue and IL-4, total IgE, and OVA-specific IgE levels in bronchoalveolar lavage fluid. However, pre-treatment of SMX did not show any effects on allergic airway inflammation. These results indicate that parasitic infection has protective effects on allergic asthma, but the sulfamamides may not relate with allergic asthma.

The regulatory effect of AST cream on atopic dermatitis-like skin disease.

  • Han, Na-Ra;Kim, Hyung-Min;Jeong, Hyun-Ja
    • CELLMED
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    • v.9 no.3
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    • pp.7.1-7.4
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    • 2019
  • In this study, we investigated an inhibitory effect of AST cream on atopic dermatitis (AD) using a 2,4-dinitrochlorobenzene-induced AD murine model. Topical treatment with AST cream ameliorated the severity of AD-like lesional skin through decreases in infiltration of inflammatory cells and time of scratching behaviors. Also, AST cream reduced histamine and IgE levels in serum. The protein levels of IL-4 and IL-6 in AD-like lesional skin were suppressed by AST cream. These findings suggest that AST cream would be an alternative therapeutic agent for AD-like skin diseases.

Dendritic Cell as an effective cancer immuno-cell therapy module I. : Anti-tumor effect of cultured DCs in murine leukemia model

  • In, So-Hee;Kim, Myung-Ju;Baek, So-Young;Lee, Hong-Gi;Kim, Ki-Hyun;Lee, Hyun-Ah
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.130.1-130.1
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    • 2003
  • As a potent antigen presenting cells and a powerful inducer of antigen specific immunity including cytotoxic T cell activity, dendritic cells(DCs) are being considered as a promising anti-tumor therapeutic module. Unlike solid tumors, leukemia is the hematologic malignancy involving immune effector cells. The expected usage of DCs in leukemia is the treatment of minimal residual disease(MRD) after the remission or stem cell transplantation. In this study, syngeneic leukemia cells were inoculated intra-venously into the mouse (WEHI-3 into the Balb/c), and the autologous tumor cell lysate pulsed DCs were injected as a therapeutic module twice in two weeks. (omitted)

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