• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.4
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• pp.405-411
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• 1993

Several studies have shown that phytol isolated from perilla leaf and small water dropwort (Oenanthe javanica (BL) D.C., wild type) extract reveal antirumor activities. In the present study we investigated the effect of phytol and the small water dropwort extract on the T subset in the sarcoma 180-transplanted mice in order to elucidate the immunological mechanism of antiturmor activity of these substances. The results obtained from the experiment were as follows : When phytol was injected into the sarcoma-180 transplanted mice (control), the levels of T cell and T subset by inoculation of the tumor cells were enhanced, but that of T cells in case of small water dropwort extract was similar to the control. Asialo GM1$^{＋}$ cells were increased when phytol or small water dropwort extract with injected into tumor-transplanted mice. In normal mice the number of asialo GM1$^{＋}$ cells increased with phytol injection and decreased with small water dropwort extract injection. L3T4$^{＋}$/Lyt-2$^{＋}$cell ratios were decreased when phytol was injected into tumor-transplanted mire, but increased in case of small water dropwort extract injection. In normal mice the ratios showed large decreases with phytol or small water dropwort extract injection. These results indicate that phytol or small water dropwort extract ran activate the proliferation of natural killer cells that are effector cells in tumor-bearing mice.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.1
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• pp.1-11
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• 2010

Purpose: This study was designed to investigate the antimetastatic and immunomodulating effects of extracts of Ulmus davidiana extracts(U. D. Ex.). Methods: Antimetastatic experiments were conducted in vitro and in vivo by using colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell and Hela cell. To observe the immunomodulating effects of U. D. Ex., we measured IL-6, IL-10, IL-12 and TNF-$\alpha$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of U. D. Ex. significantly inhibited tumor metastasis in vivo. In vitro cytotoxicity analysis, cell growth are closer to 100% in case of Colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell and Hela cell at low concentration. In case of macrophage, cell proliferation is closer to 100% less than $250{\mu}g/ml$ of U. D. Ex.. The level of cytokine such as IL-6, IL-10, IL-12 which stimulates U. D. Ex. was increased in dose-dependent manner compared to the control group. In case of TNF-$\alpha$, the level was increased at concentration of $1,000{\mu}g/ml$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of U. D. Ex. on tumor metastasis. Conclusion: Ulmus davidiana appears to have considerable activity on the anti-metastasis by activation the immune system.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.41-52
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• 2009

Purpose: This study was designed to investigate the anti-tumor metastasis by immunomodulating effects of extracts of Prunellae Spica. Methods: Antimetastatic experiment was conducted in vivo by using colon 26-M3.1 carcinoma. And we observed cytotoxicity of Prunellae Spica on colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell and macrophage. To observe the immnomodulating effects of Prunellae Spica, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Prunellae Spica extracts significantly inhibited tumor metastasis in vivo. In an in vitro cytotoxicity analysis, cell growth are closer to 100% in case of colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell at low concentration. In case of macrophage, cell proliferation is closer to 100% less than $62.5{\mu}g/m{\ell}$ of Prunellae Spica extracts. The level of cytokine such as IL-6, IL-10, IL-12 which stimulates Prunellae Spica extracts was increased in dose-dependent manner compared to the control group. TNF-${\alpha}$ is hardly secreted less than $250{\mu}g/m{\ell}$ The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Prunellae Spica on tumor metastasis. Conclusion: Prunellae Spica appears to have considerable activity on the anti-metastasis by activation the immune system such as macrophage and NK cell.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.31-40
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• 2009

Purpose: This study was carried out to investigate the anti-tumor metastasis effect and activation of innate immunity by extracts of Mori radicis cortex. Methods: Anti-tumor metastatic experiment was conducted in vitro and in vivo by using colon 26-M3.1 carcinoma cell, L5178Y-R lymphoma cell and HeLa cell. To observe the activation of innate immunity by extracts of Mori radicis cortex, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Mori radicis cortex extracts significantly inhibited tumor metastasis. In an in vitro cytotoxicity analysis, Mori radicis cortex affected tumor cell growth above specific concentration. Mori radicis cortex also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-6, IL-10, IL-12, TNF-${\alpha}$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Mori radicis cortex on tumor metastasis. Conclusion: Mori radicis cortex appears to have considerable activity on the anti-metastasis by activation of innate immunity.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.218-222
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• 2009

Ability of water extract from Prunella vulgaris Labiatae to stimulate immune system and inhibit tumor metastasis in mice was assessed. In experimental lung metastasis, prophylactic intravenous (i.v.) administration of water extract from P. vulgaris significantly inhibited lung metastasis in a dose-dependant manner. Peritoneal macrophages stimulated with P. vulgaris produced various cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-12 as well as induced tumoricidal activity. In an assay for natural killer (NK) cell activity, i.v. administration of P. vulgaris significantly augmented NK cytotoxicity. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of P. vulgaris on lung metastasis of colon26-M3.1 cells. These data demonstrate that P. vulgaris activate innate immune system to inhibit the growth of foreign materials including tumor cells in mice.

• BMB Reports
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• v.52 no.9
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• pp.554-559
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• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.4
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• pp.1-14
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• 2014

Objectives: This study was designed to investigate the anti-tumor metastasis by anti-inflammatory and innate immunomodulating effects of extracts of Jipae-san on cancer cells. Methods: Antimetastatic experiments were conducted in vivo mouse model by using 4T1 mouse mammary carcinoma cells. Cell viability of Jipae-san was tested with 4T1 mouse mammary carcinoma cells, colon 26-M3.1 carcinoma cells and macrophage. In addition expression of $TNF-{\alpha}$ and NO induced by LPS was measured after treating with Jipae-san. To observe innate immunomodulating effects of Jipae-san on macrophage, we measured $TNF-{\alpha}$, IL-12, IL-6 and MCP-1, respectively. Cell cytotoxicity was tested with the macrophage stimulated with Jipae-san and we evaluated the activation of $TNF-{\alpha}$ and NO. And the effect of Jipae-san on metastasis was measured without NK-cell using GM1 serum. Results: Intravenous inoculation of Jipae-san significantly inhibited metastasis of 4T1 mouse mammary carcinoma cells. In an in vitro cytotoxicity analysis, cell growth are closer to 100% less than $1,000{\mu}g/ml$ concentration. The expression of $TNF-{\alpha}$ and NO induced by LPS after treating Jipae-san was down regulated in dose-dependent manner. Level of cytokines such as $TNF-{\alpha}$, IL-12, IL-6 and MCP-1 of Jipae-san group were up regulated in compared to the control group. The macrophage stimulated with Jipae-san significantly inhibits the cancer cell at ratio of 10:1, 20:1. The activation of NO was significantly up regualted in a group of 5:1, 10:1, 20:1. The depletion of NK-cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Jipae-san on tumor metastasis. Conclusions: Jipae-san appears to have considerable activity on the anti-metastasis by inflammation control and activation of innate immune system.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.217-224
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• 2004

Previously, we reported that water-extracted Acanthopanax senticasus exhibited anti-meta-static activity by stimulating the immune system. In this study, we fractionated glycoproteins (EN-SP) from the soluble protein layer (GF-AS) of A. senticasus and determined their basic chemical properties. We also investigated the anti-tumor and immunostimulating activities of the fractionated glycoprotein, EN-SP. We found that intravenous (i.v.) administration of GF-AS dramatically inhibited metastasis of colon26-M3.1 carcinoma cells to the lung in a dose-dependent manner. In vitro analysis showed GF-AS to enhance the proliferation of splenocytes. GF-AS also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-1$\beta$, TNF-$\alpha$, IL-12 and IFN-${\gamma}$. Furthermore, the production of these cytokines was partially blocked when peritoneal macrophage was cultured with the polyclonal antibodies against GF-AS. The depletion of NK cells by rabbit anti-asialo GM1 serum partly abolished the inhibitory effect of GF-AS on lung metastasis of colon26-M3.1 cells. Using gel filtration, EN-SP, an active glycoprotein fraction, is isolated from GF-AS. While both GF-AS and EN-SP stimulated the proliferatation of splenocytes of normal mice, EN-SP showed higher anti-metastatic activity and more potently stimulated the proliferation of splenocytes compared to GF-AS. These results suggest the use of EN-SP, the fractionated glycoprotein from A. senticasus, can be used as a therapeutical reagent to prevent or inhibit tumor metastasis.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.4
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• pp.10-19
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• 2010

Methods: Intravenous administration of Platycodon grandiflorum was performed 2 days before tumor inoculation, then mice were killed 14 days after tumor inoculation, then number of tumor colonies were counted. Methanol extracts of Platycodon grandiflorum was added to colon26-M3.1 carcinoma cells, L5178Y-R lymphoma cells and Hela cells, and then cell growth was counted. To observe the immunomodulating effects of Platycodon grandiflorum, production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were measured with ELISA assay and the cell growth of macrophage were also counted. Furthermore, antimetastatic experiment after depletion NK cells by injection of anti-asialo GM1 serum was also administered. Results: Intravenous administration of Platycodon grandiflorum significantly inhibited metastasis of colon26-M3.1 carcinoma cells. In an in vitro cytotoxicity analysis, Platycodon grandiflorum affected tumor cell growth above specific concentration. As compared with control, the production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were incresed. And depletion NK cell completly abolished the inhibitory effect of metastasis. Conclusion: Platycodon grandiflorum appears to have considerable activity on immunomodulating effects and inhibit the metastasis of tumor. Further evaluation is needed for settling this.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.