• Title/Summary/Keyword: $\alpha$-CD

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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.

A Study on the Effect of Luffae Fructus Retinervus Herbal-Acupuncture at ST36 on Collagen-induced Arthritis in Mice (족삼리(足三里) 사과락약침(絲瓜絡藥鍼)이 생쥐의 Collagen-induccd Arthritis에 미치는 영향)

  • Chae, Choong-heon;Choi, Sun-mi;Yim, Yun-kyoung
    • Journal of Acupuncture Research
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    • v.22 no.1
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    • pp.131-144
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    • 2005
  • Objective : The aim of this study is to observe the effect of Herbal-acupuncture(HA) with Luffae Fructus Retinervus Herbal-Acupuncture Solution(LFR-HAS) at ST36(Joksamni) on Collagen Ⅱ -induced arthritis(CIA) in mice. Methods : DBA1/J mice were immunized with bovine type Ⅱ collagen(CⅡ) on days 0 and 21 to induce an arthritis. The mice were divided into 5 groups. They were Normal group(wild type), Control group(CIA), Saline group(CIA +saline injection), Needle Prick group(CIA +single Prick with an injection needle) and LFR-HA group(CIA +LFR-HA treatment). The saline injection, needle prick and LFR-HA were made on the right ST36(Joksamni) of mice for 5 weeks, 3 times a week beginning 4 weeks after the booster immunization. Results : 1. The highest synovial rate of lung fibroblasts was measured in the 1% LFR-HAS. 2. TNF-${\alpha}$ expression of survival cells from CIA mouse joint was significantly reduced in the 1% LFR-HAS. 3. The incidence of arthritis and the spleen weight of CIA mouse were significantly reduced by the Luffae Fructus Retinervus Herbal-Acupuncture (LFR-HA) at ST36. 4. The concentrations of IL-6, INF-${\alpha}$, INF-${\alpha}$, IgG, IgM, and anti-collagen Ⅱ in the CIA mouse serum were significantly reduced by the LFR-HA at ST36. 5. The histological examination showed that, in the LFR-HA group, the cartilage destruction and the synoviocyte proliferation in the CIA mouse joint were not significant compared to the control group, and the collagen fiber was similarly expressed as the normal group. 6. In the LFR-HA group, the ratio of CD3e+ to CD19+ cell, and the ratio of CD4+ to CD8+ cell in the lymph node were similarly maintained as those of the normal group. 7. CD69+/CD3e+ and CD11a+/CD19+ cells in the CIA mouse lymph node were significantly reduced by the LFR-HA at ST36. 8. CD11b+/Gr-1+ cells in the CIA mouse joint were significantly reduced by the LFR-HA at ST36. Conclusions : These results indicate that Luffae Fructus Retinervus Herbal-Acupuncture (LFR-HA) at ST36 may regulate the immune system and have a therapeutic effect on Collagen-induced arthritis(CIA) in mice.

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Effects of Capsosiphon Fulvescens Extract on Contact Dermatitis in NC/Nga Mice (매생이(莓山苔) 추출물이 NC/Nga 마우스의 접촉성 피부염에 미치는 효과)

  • Eom, Ye-Jin;Hong, Chul-Hee
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.30 no.4
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    • pp.25-36
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    • 2017
  • Objectives : The aim of this study is to report the effect of Capsosiphon fulvescens(Maesangi) extract(MSE) on contact dermatitis(CD). Methods : CD induced by Dermatophagoides farinae body(Dfb) in NC/Nga mice. 4% sodium dodecyl sulfate(SDS) $150{\mu}l$ and Dfb(10mg/ml) ointment 100mg were topically treated twice a week for four weeks. MSE 200 mg/kg was topically treated every 4weeks. Every week, we examined the skin lesions, weight of spleen and lymph node, epidermal thickness, production of Tumor necrosis factor-alpha($TNF-{\alpha}$) and interleukin-6(IL-6). Results : MSE reduced features of Dfb-induced skin lesions, weight of spleen and production of $TNF-{\alpha}$. MSE significantly reduced weight of lymph node, epidermal thickness, number of mast cells and production of IL-6. Conclusions : MSE may have a potential therapeutic effects for CD by suppressing allergic inflammation.

Reaction Mechanism of Transglycosylation of Stevioside in the Attrition Coupled Reaction System Using Raw Starch as a Glycosyl Donor (생전분을 당공여체로 한 분쇄마찰매체 함유 효소반응계에서의 Stevioside의 당전이 반응 기작)

  • Baek, Seung-Gul;Park, Dong-Chan;Huh, Tae-Lin;Lee, Yong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.22 no.3
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    • pp.252-258
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    • 1994
  • Transglycosylation of stevioside in the attrition coupled heterogeneous reaction system using raw starch as a glycosyl donor has significant advantages over conventional reaction systems using liquefied starch as a donor. The transglycosylation of stevioside under the presence of organic solvent showed that transglycosylation reaction occurs via two steps ; initially from raw starch to cyclodextrin(CD), and then followed by transglycosylation of produced CD. Comparison of the transglycosylation efficiency of c$\alpha $-, $\beta $, $\gamma $-CDs indicated that $\alpha $-, $\beta $-CD are mainly utilized as a glycosyl donor for following reaction. The reaction mechanism of transglycosylation between stevioside and CD proceeded according to random sequential bireactant mechanism. The equilibrium constant of transglycosylation reaction of cyclodextrin glucanotransferase wase also evaluated. The structure of transglycosylated stevioside was confirmed by TLC, and it was found that glycosyl group(G$_{1}, $ ~ G$_{4}$-glycosidic bond.

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Immunoregulative Action of Ethyl Alcohol Fraction of Cervus nippon (녹용 에탄올 분획의 면역조절작용)

  • Suh, Jeong-Sook;Kwon, Jin
    • The Korean Journal of Food And Nutrition
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    • v.14 no.2
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    • pp.99-105
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    • 2001
  • Immunoregulative action of 70% ethyl alcohol fraction of Cervus nippon was investigated in vitro. The fraction enhanced the proliferation of thymocytes and the population of CD4$\^$+/CD8$\^$-/ single-positive cells in thymocytes. CN-E enhanced [Ca$\^$2+]$\sub$i/, the production of TNF-${\alpha}$ and IL-1 ${\beta}$, and phagocytosis in peritoneal macrophages. The fraction did not induce the proliferation of splenocytes and DNA fragmentation in thymocytes. These results indicate that 70% ethyl alcohol fraction of Cervus nippon regulates immunological action by stimulating murine thymocytes and macrophages.

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Predominant T Helper 1 Immune Response in Women with Reproductive Failures (반복 유산 및 착상실패를 보이는 환자에서 Th1 면역반응에 대한 연구)

  • Han, Ae-Ra;Yang, Kwang-Moon;KwakKim, Joanne
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.3
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    • pp.231-237
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    • 2010
  • Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

The Effects of Dictamni Radicis Cortex Extracts on DNCB Induced Atopic Dermatitis-like Skin Lesions of NC/Nga Mouse (백선피(白鮮皮) 추출물이 DNCB로 유발된 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Lee, Youn Shil;Han, Jae Kyung;Kim, Yun Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.4
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    • pp.1-29
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    • 2014
  • Objectives Dictamni Radicis Cortex extracts (DRC) has been known to suppress allergic reaction, however the cellular target of DRC and its mode of action remain unclear. The purpose of this study is to investigate the effects of Dictamni Radicis Cortex extracts on DNCB induced atopic dermatitis-like skin lesions of NC/Nga mouse. Methods This study was designed to investigate the effects of DRC extract in the DNP-IgE-induced activation of MC/9 murine mast cell lines in vitro and in the DNCB-induced activation of NC/Nga mouse in vivo. For this investigation, We examined IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA analysis and manifestations of NFAT1, NFAT2, AP-1 and NF-${\kappa}B$ p65 transcription factors by western blotting in vitro. Then, we examined WBC, eosinophil and neutrophil in NC/Nga mouse, IL-5, IL-13 in serum, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $^+Gr-1^+CD11b$, $B220^+CD23^+$ in the ALN, PBMCs and dorsal skin, IL-5, IL-13 in the dorsal skin by Real-time PCR and the distribution of mast cells by H&E and toluidine blue. Results In vitro the mRNA expression of IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$, GM-CSF and IL-13, MIP-$1{\alpha}$ production by ELISA analysis were completely abolished by DRC and the western blot analysis decreased the expression of mast cell-specific transcription factors including NFAT-1, NF-${\kappa}B$ p65. In vivo DRC oral adminstration also decreased the counts of WBC, eosinophils and inflammatory cytokines such as IL-13 and IgE in the serum. DRC oral adminstration elevated IL-4 level in the spleenocyte culture supernatant. DRC oral adminstration decreased total ALN cells, total skin cells, cell numbers of $CD4^+$, $B220^+CD23^+$ in the ALN, $^+Gr-1^+CD11b$ in the PBMCs and $CD4^+$, $CD8^+$ in the dorsal skin. The mRNA expression of IL-5, IL-13, thickness of epidermis, inflammation immune cells and mast cells were abolished by DRC in the dorsal skin. Conclusions Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mouse were much improved by DRC oral adminstration. These results, therefore, suggest that DRC can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mouse, and may play an important role in recovering AD symptoms.

Comparisons of C-kit, DOG1, CD34, PKC-θ and PDGFR-α Expressions in Gastrointestinal Stromal Tumors According to Histopathological Risk Classification

  • Kim, Ki-Sung;Song, Hye-Jung;Shin, Won-Sub;Song, Kang-Won
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.2
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    • pp.48-56
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    • 2011
  • Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor and is associated with a specific immunophenotype index. It is very important to identify the specific immunophenotype and the diagnosis for the treatment GIST patients. Ninety two cases of GIST analyzed in this study were immuno-stained for c-kit, DOG1, CD34, PKC-${\theta}$, PDGFR-${\alpha}$. The rate of positive staining and statistical significance were then compared. In addition, the GISTs were analyzed as followings: very low risk, low risk, intermediate risk and high risk according to tumor size and nuclear division, and later correlated with clinical parameters. The results of the GIST positive stainings were: DOG1 (95.7%), PKC-${\theta}$ (90.2%), PDGFR-${\alpha}$ (88.0%), c-kit (87.0%) and CD34 (71.7%). Only DOG1 staining showed a statistical significance of p<0.05. It was identified in the classification system of histologic risk that staining expression of DOG1, PKC-${\theta}$, PDGFR-${\alpha}$ were significantly increased as histologic risk increases (p<0.05). However, clinical parameters such as age and sex of patients have no correlations with the classification system of histologic risk (p>0.05). Therefore, in this study, the expression of DOG1 showed statistical significance and DOG1, PKC-${\theta}$, PDGFR-${\alpha}$ staining increased significantly as the histologic risk increases in histologic classification system. Taken together, the DOG1 staining should be very effective for the diagnosis of GIST patients.

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Immune-modulator Effect of Zanthoxyli Pericarpium Watet Extract (천초 추출물의 면역 조절 효과)

  • Shin, Hye-Young;Chang, In-Ae;Zhang, Wen-Ji;Kim, Youn-Chul;Yun, Yong-Gab;Park, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.2
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    • pp.410-414
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    • 2008
  • In the recently, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the modulatory effects of the extract of Zanthoxyli Pericarpium (ZP) in production of inflammatory mediators from Raw264.7 cells and expression of CD86, CD14, toll-like receptor (TLR)-4 from peritoneal macrophage. ZP enhanced the production of NO and $TNF-{\alpha}$ as well as mRNA expression of iNOS and $TNF-{\alpha}$. Treatment of peritoneal macrophage with ZP resulted in the enhanced cell-surface molecules expression of CD86, CD14 and TLR4. We assayed the effect of ZP in cell proliferation and production of $IFN-{\gamma},\;TNF-{\alpha}$. ZP increased Con A-induced cell proliferation and production of $IFN-{\gamma},\;TNF-{\alpha}$. These studies indicate that ZP induces macrophage activation and suggest the possible use of ZP in macrophage-based immunotherapies

Sensitivity Enhancement of Polydiacetylene Vesicles through Control of Particle Size and Polymerization Temperature (입자크기와 중합온도 제어를 통한 폴리다이아세틸렌의 센싱감도 향상)

  • Lee, Gil Sun;Oh, Jae Ho;Ahn, Dong June
    • Korean Chemical Engineering Research
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    • v.49 no.4
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    • pp.400-404
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    • 2011
  • Many studies on polydiacetylene(PDA) have been investigated to apply to chemical and biological sensors due to their unique optical properties of color change from blue to red and fluorescence change from non-fluorescence to red fluorescence. Especially, high sensitivity against specific molecules is very important to apply polydiacetylenes to various sensors. In this study, we examined the effect of sensitivity enhancement of 10,12-pentacosadynoic acid(PCDA) vesicles in detection ${\alpha}$-cyclodextrin(CD) according to control of vesicle size by filters with different pore sizes and polymerization temperature. Colorimetric response(CR) was calculated using visible spectrometer. In order to investigate the effect of vesicle size on sensitivity of PDA vesicles, two PCDA vesicles were filtered without filtration and with 0.22 ${\mu}m$ filter. The two PCDA vesicles were polymerized at $25^{\circ}C$ and were incubated with ${\alpha}$-CD(5 mM) for 30 min. The CRs of the former and latter vesicles were 31.4% and 74.0%, respectively. Then, two PCDA vesicles filtered with 0.22 ${\mu}m$ filter were polymerized at $25^{\circ}C$ and $5^{\circ}C$ and were reacted with ${\alpha}$-CD(5 mM) for 30 min to examine the effect of polymerization temperature. The CRs of the former and latter vesicles were 74.0 and 99.2%, respectively. This suggests that vesicle sizes and polymerization temperature are key factors in enhancing the sensitivity of PDA vesicles. In addition, these results are expected to be useful to apply the PDA vesicles as biosensors to detect DNA, protein, and cells.