• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2101-2105
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• 2013

Background: Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. Materials and Methods: Efficacy and safety profiles of sunitinib after interferon alpha (IFN-${\alpha}$) were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. Results: Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs $NLR{\leq}3$ (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs $NLR{\leq}3$ (p:0.001).While 75% of patients who responded to sunitinib had $NLR{\leq}3$, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). Conclusions: Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-${\alpha}$ to be effective and tolerable. NLRappeared to have prognostic and predictive value.

• 생명과학회지
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• 제19권3호
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• pp.411-416
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• 2009

본 연구에서는 키토산이 마우스에서 Th1과 Th2 사이토카인의 생성에 미치는 효과를 보기 위하여 키토산에 의한 IL-2 생성의 변화, 키토산에 의한 IFN-$\gamma$ 생성의 변화, 그리고 키토산에 의한 IL-4 생성의 변화, 키토산에 의한 IL-10 생성의 변화를 시험관내에서 시험하였다. 또한 LPS, Con A, PHA-P와 같은 세포자극물과 키토산이 함께 작용되었을 때 상기 사이토카인의 생성의 변화를 관찰하였다. 키토산을 비장세포에 노출시켰을 때 Th1 사이토카인인 IL-2와 IFN-$\gamma$의 생성이 크게 증가하였지만 고농도의 키토산에 의해서는 오히려 대조군에 비하여 감소하였다. LPS와 같은 세균독소, Con A와 같은 세포자극물을 비장세포에 노출시켰을 때 IL-2와 IFN-$\gamma$의 생성은 큰 상승을 나타냈으며 LPS의 경우 키토산에 의해서 IL-2와 IFN-$\gamma$의 생성이 증폭되었다. 키토산을 비장세포에 노출시켰을 때 Th2 사이토카인인 IL-4와 IL-10의 생성은 큰 증가를 보이지 않았다. LPS와 같은 세균독소에 의한 IL-4와 IL-10의 상승이 키토산에 의해서 억제되었다. 따라서 이러한 결과들로 부터 키토산이 LPS와 같은 세균독소가 존재하는 가운데 Th1 사이토카인을 증가시키고 Th2 사이토카인을 감소시킴에 따른 면역반응 환경이 이루어질 가능성이 높다 하겠다. 앞으로 키토산에 대한 더 많은 자료의 축적이 이루어지게 되면 임상에서 Th1/Th2 면역반응의 균형을 유지하는데 이용될 가능성도 있다 하겠다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3961-3968
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• 2015

Background: Variants of human papillomavirus (HPV) show more oncogenicity than do prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16 variants affect E6 functions such as p53 interaction and host immune surveillance. This study aimed to investigate activities of HPV16As E6 protein on modulation of expression of miRNA-21 as well as interferon regulatory factors (IRFs) 1, 3, 7 and c-fos. Materials and Methods: Vectors expressing E6 protein of HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of E6 and proliferation of the transfected C33A cells were determined. MiR-21 and mRNA of interesting genes were detected in the transfected C33A cells and/or the HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa-CM). Results: E6D25E showed binding activity with E6AP similar to that of E6Pro. Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro in C33A cells expressing E6 protein. This result was similar to the HCK1T cells expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation significantly corresponded to its target expression. Different levels of expression of IRFs were also observed in the HCK1T cells expressing E6 protein. Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in the HCK1T cells expressing E6Pro were induced. A similar situation was seen for IFN-${\alpha}$ and IFN-${\beta}$. Conclusions: E6D25E of the HPV16As variant differed from the E6 prototype in its activities on epigenetic modulation and immune surveillance and this might be a key factor for the important role of this variant in cervical cancer progression.

• 식품산업과 영양
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• 제9권1호
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• pp.36-45
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• 2004

Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.

• International Journal of Oral Biology
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• 제33권4호
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• pp.163-177
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• 2008

Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 ($fimA^-$), CW120 ($ppk^-$) and KS7 ($relA^-$) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-$1{\beta}$ and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon-$\gamma$-inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.

• Toxicological Research
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• 제22권4호
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• pp.357-364
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• 2006

This study was undertaken to develop a reliable mice model demonstrating similar immunologic phenomena as human atopic dermatitis characterized with predominance of type-2 immune response. BALB/C mice and NC/Nga mice were sensitized twice with $100{\mu}l$ of 1% 2,4-dinitrochlorobenzene (DNCB) or vehicle (acetone : olive oil=4:1 mixture) in a week and challenged twice with $100{\mu}l$ of 0.2% DNCB or the vehicle at the following week. Mice were sacrificed at 19 days following the second DNCB or vehicle challenge for NC/Nga mice and at 28 days following the second DNCB or vehicle challenge for BALB/c mice. Upregulation of plasma 1gE, a hallmark of atopic dermatitis occurrence, was evident in the plasma obtained 4 day after the second DNCB challenge from BALB/c mice (approximately 4-fold) and NC/Nga mice (approximately 6-fold) treated with DNCB in comparison with that of the vehicle treated-control mice, and remain higher $3{\sim}4$ week after the second challenge. Ratio of plasma IgG1 versus IgG2a concentration was significantly higher in the mice treated with DNCB than the control mice, which also implies the skewed type-2 reactivity in vivo. Ratio of interleukin-4 versus interferon gamma produced in the splenic T cell culture supernatants was approximately 3-fold higher in the both strains of mice treated with DNCB than their control mice, respectively. The DNCB-treated mice demonstrated atopic dermatitis-like skin legions characterized with erythma, scaling, and hemorrhage, which was not observed with the control mice. Scratching on face or dorsal area was significantly more frequent (approximately 25-fold) in the DNCB-treated mice than the control at next day of the second DNCB challenge, and scratching frequency remains higher (approximately 4-fold) in the mice treated with DNCB than the control at 14 day following the second DNCB challenge. Overall, the mice model developed through sensitization and challenge with DNCB may be useful for research on atopic dermatitis and development of treatment materials for atopic dermatitis.

• 생명과학회지
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• 제18권12호
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• pp.1637-1643
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• 2008

HSP90에 노출된 혈관평활근세포에서 IL-6 transcript가 증가하고, IL-6 단백질의 분비가 증가하며, 또한 IL-6 유전자의 promote가 활성화되었다. HSP90에 의한 IL-6 유전자의 promoter 활성화는 dominant negative 형태의 TLR-4와 MyD88에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-3와 TRIF의 영향을 받지 않았다. 그리고 TLR-4의 이합체화(dimerization)를 저해하는 curcumin은 HSP90에 의한 IL-6의 분비 및 IL-6 유전자 promoter 활성화를 억제하였다. 그리고 IL-6 유전자의 promoter의 NF-${\kappa}B$- 또는 C/EBP-binding sequence에 변이는 HSP90에 의한 IL-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 IL-6 유전자 활성화에 TLR-4와 NF-${\kappa}B$B가 관여함을 의미한다.

• 한국식품과학회지
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• 제42권1호
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• pp.109-114
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• 2010

결명자(Cassia obtusifolia) 및 포공영(Taraxacum platycarpum), 유근피(Ulmus macrocarpa)로 제조된 생약재 추출혼합물이 in vitro와 in vivo상에서 아토피 피부염에 미치는 영향을 실험하였다. HMC-1 cell을 이용하여 비만세포의 $\beta$-hexosaminidase 방출량을 측정한 결과, 단일 추출물보다 추출복합물이 탈과립을 억제하는 효과가 우수한 것으로 측정되었다. 그리고 HMC-1 cell에서 PMA와 A23187로 자극하였을 때 생성되는 염증성 cytokine의 분비에서도 추출혼합물의 저해 효과가 가장 높게 나타났다. 아토피 질환모델인 NC/Nga 마우스를 사용하여 생약재 추출혼합물의 아토피 저감효과를 측정한 결과, 진드기 추출물에 의해 발진된 마우스의 귀두께 및 조직학적인 부종 관찰을 통해 생약재 추출혼합물 농도가 증가함에 따라 대조군에 비해 귀 두께 및 부종의 감소가 관찰되었다. 또한 마우스의 혈중 IgE 농도와 이와 관련된 cytokine의 농도를 측정한 결과, 생약재 추출혼합물 투여농도가 증가함에 따라 IgE의 농도가 유의적으로 감소하였고, IgE의 과발현을 유도하는 IL-4의 분비 억제 및 IFN-$\gamma$의 분비가 증가되는 것으로 나타나 생약재 혼합추출물의 섭취가 아토피 피부염 증세 완화 효과에 도움이 되리라 사료된다.

• Journal of Ginseng Research
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• 제40권1호
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.

• 대한예방한의학회지
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• 제6권2호
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• pp.156-167
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• 2002

This experimental study was carried out to evaluate the effects of Kimchi intake of Cordyceps sinensis extract (CDSE) supplementation on cytokine-induction and immune response in mice. To study in experiments using male Balb/c mice fed Kimchi and Kimchi of CDSE supplementation (addition of 2% of total Kimchi weight) containing fed experimental diet during 2 weeks. Experimental mice were fed control diet or diet containing freeze-dried Kimchi at the level of 5%(w/w) or 5% freeze-dried Kimchi with 2% CDSE supplementation. The main ingredient of Kimchi was Korean cabbage and fermentation was carried out at $4^{\circ}C$ for three weeks. Freeze-dried 2% CDSE supplementation was added to Kimchi at the beginning of fennentation. In order to investigate the effect of Kimchi intake of CDSE supplementation (5%Kimchi-2%CDSE), the following was performed; body weight, food intake, hematological parameter, serum level of mouse interleukin-4 (mIL-4) and mouse $interferon-{\gamma}$ $(mIFN-{\gamma})$, and, the percentage of CD3+/CD4+, CD3+/CD8+, B220+ in splenic cells. The results of final body weight, and food diet intake of two Kimchi groups were lower than those of the control group (not supplemented experimental diet). The hematology change obtained from the level of WBC (white blood cell) and platelet were not affected by feeding different dietary regiments, but the level of RBC (red blood cells) HB (hemoglobin), and spleen weight of two Kimchi groups were increased significantly than those of the control group. The serum level of IL-4 and $IFN-{\gamma}$ of two Kimchi groups were increased significantly than those of the control group, also enhanced the percentages of the CD3+/CD4+ and CD3+/CD8+ by 5% freeze-dried Kimchi, and 5%Kimchi-2%CDSE group were 43.9 and 60.1%, and 96.0 and 174% than those of the control group, respectively. From these results, it can be concluded that Kimchi itself has an immuno-stimulatory effect and Kimchi contaning 2% CDSE supplementation has the more pronounced effect in vivo system.