• 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.

• Journal of the Korean Society of Radiology
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• v.82 no.4
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• pp.903-913
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• 2021

Purpose To identify the imaging features indicative of sarcoid-like reactions in patients with intrathoracic lymphadenopathy after complete remission of malignancies. Materials and Methods This study enrolled five patients with histopathologically confirmed sarcoid-like reactions that developed after cancer remission. The clinical features and findings of CT and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT were assessed. Results The underlying malignancies included breast, nasopharyngeal, colon, and endometrial cancer and lymphoma. The time intervals between complete remission of malignancy and the diagnosis of sarcoid-like reaction ranged from 6 to 78 months. CT findings of sarcoid-like reaction included bilateral hilar and mediastinal lymphadenopathies (n = 5), pulmonary nodules (1-15 mm) with peribronchovascular, fissural, or subpleural distribution, and interlobular interstitial thickening in the lungs (n = 4). ¹⁸F-FDG PET/CT revealed hypermetabolic uptake in the mediastinal and hilar lymph nodes and both lungs in the absence of extrathoracic uptake (n = 3). The sarcoid-like reactions resolved in all patients after corticosteroid treatment. Conclusion In patients with complete remission of malignancies, newly developed bilateral hilar and mediastinal lymphadenopathies with or without pulmonary nodules of perilymphatic distribution, in the absence of recurrence at the primary tumor site and extrathoracic metastasis, may suggest a sarcoid-like reaction. Such cases warrant histologic evaluation of the lymph nodes to prevent unnecessary systemic chemotherapy.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.

• Journal of Microbiology and Biotechnology
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• v.24 no.12
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• pp.1654-1663
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• 2014

To examine the effect of tumor suppressor protein p53 on the antitumor activity of 2-methoxyestradiol (2-MeO-$E_2$), 2-MeO-$E_2$-induced cell cycle changes and apoptotic events were compared between the human colon carcinoma cell lines HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$). When both cell types were exposed to 2-MeO-$E_2$, a reduction in the cell viability and an enhancement in the proportions of $G_2/M$ cells and apoptotic sub-$G_1$ cells commonly occurred dose-dependently. These 2-MeO-$E_2$-induced cellular changes, except for $G_2/M$ arrest, appeared to be more apparent in the presence of p53. Immunofluorescence microscopic analysis using anti-${\alpha}$-tubulin and anti-lamin B2 antibodies revealed that after 2-MeO-$E_2$ treatment, impaired mitotic spindle network and prometaphase arrest occurred similarly in both cell types. Following 2-MeO-$E_2$ treatment, only HCT116 ($p53^{+/+}$) cells exhibited an enhancement in the levels of p53, p-p53 (Ser-15), $p21^{WAF1/CIP1}$, and Bax; however, the Bak level remained relatively constant in both cell types, and the Bcl-2 level decreased only in HCT116 ($p53^{+/+}$) cells. Additionally, mitochondrial apoptotic events, including the activation of Bak and Bax, loss of ${\Delta}{\psi}m$, activation of caspase-9 and -3, and cleavage of lamin A/C, were more dominantly induced in the presence of p53. The Bak-specific and Bax-specific siRNA approaches confirmed the necessity of both Bak and Bax activations for the 2-MeO-$E_2$-induced apoptosis in HCT116 cells. These results show that among 2-MeO-$E_2$-induced apoptotic events, including prometaphase arrest, up-regulation of Bax level, down-regulation of Bcl-2 level, activation of both Bak and Bax, and mitochondria-dependent caspase activation, the modulation of Bax and Bcl-2 levels is the target of the pro-apoptotic action of p53.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.351-355
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• 2010

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.

• Journal of Dairy Science and Biotechnology
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• v.32 no.2
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• pp.141-145
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• 2014

There is a burgeoning number of products on the market that contain probiotics, but do they do you any good? What exactly are probiotics? They have been defined as living organisms that, when ingested in sufficient quantities, provide health benefits beyond basic nutrition. They are often referred to as "friendly bacteria" or "good bacteria." Probiotics have been claimed, amongst other things, to (i) reduce the incidence of colon cancer and other diseases of the colon, such as IBS, (ii) stimulate the immune system, (iii) have anti-hypertensive and anti-cholesterolemic properties, (iv) mitigate against the effect of antibiotics on the intestinal microbiota, and (v) protect against gastrointestinal infections. However, the scientific basis for many of these claims is not well-established. Indeed, the European Food Safety Authority has denied the use of several health claims associated with probiotics, particularly those related to mitigation of diarrhea following consumption of antibiotics. Thus, there is a need for research on the mechanisms of action of probiotics. We have been mainly interested in the use of probiotics to control enteric infections. There are several possible modes of action to explain how probiotics may protect the host from enteric pathogens, including competitive exclusion and immunomodulation. We have shown that probiotics produce bioactive molecules that interfere with bacterial cell-cell communication (also called quorum sensing), and this results in a down-regulation of virulence genes that are responsible for attachment of the pathogen to the gastrointestinal epithelium. These bioactive molecules act on a variety of bacteria, including enterohemorrhagic and enterotoxigenic Escherichia coli, Salmonella, Clostridium difficile and Clostridium perfringens, and there is evidence that they can inhibit the formation of biofilms by Listeria monocytogenes. These bioactive molecules, which are peptidic in nature, can exert their effects not only in vitro but also in vivo, and we have shown that they mitigate against E. coli O157:H7 and Salmonella in mice and Salmonella and E. coli K88 infections in pigs. They can be delivered in foods such as yoghurt and maintain their activity.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.7
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• pp.832-838
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• 2009

The inhibitory effects of solvent extracts from dried beet (Beta vulgaris) on $H_2O_2$-induced oxidative stress in cell systems and on the growth of cancer cell lines (HT-29 human colon cancer and AGS human gastric adenocarcinoma cells) were investigated. Inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts on the growth of HT-29 and AGS cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was more significant on the growth of AGS cells and A+M extracts had a higher inhibitory effect compared to MeOH extracts. The treatments of hexane, 85% aq. methanol, butanol and water fractions significantly inhibited the growth of both cancer cells (p<0.05). Among fractions, hexane and 85% aq. methanol fractions showed higher inhibitory effects. In order to determine the protective effect on $H_2O_2$-induced oxidative stress, DCHF-DA (dichlorodihydrofluorescin diacetate) assay was conducted. The A+M and MeOH extracts of dried beet appeared to significantly reduce the levels of intracellular (ROS) with dose responses. Among the fractions, 85% methanol fractions showed a higher protective effect on production of lipid peroxides. These results indicate that the intake of dried beet may improve oxidative stress in cell and reduce cancer risk.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Journal of Life Science
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• v.19 no.12
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• pp.1737-1742
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• 2009

It has been known that Linum usitatissimum and Perilla frutescens are dietary sources of possible chemopreventive compounds such as lignans and $\alpha$-linolenic acid. Here, we investigated and compared the inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on mutagenicity using the Ames test, and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatment with the methanol extract from either Linum usitatissimum or Perilla frutescens (p<0.05) in a dose dependent manner. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from Linum usitatissimum and Perilla frutescens showed 63% and 78% inhibitory rates, respectively, indicating that Perilla frutescens possessed stronger antimutagenic activity than did Linum usitatissimum. Inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on the growth of human cancer cells (AGS, HT-29 and Hep 3B) appeared to increase dose dependently, and the inhibition was more effective against AGS and HT-29 compared to Hep 3B cells. Our results suggested that the methanol extract from Perilla frutescens showed stronger antimutagenic activity than that from Linum usitatissimumas assayed by the Ames mutagenic test, whereas the methanol extract from Linum usitatissimum was more effective than its counterpart for growth inhibition of human cancer cells. It is concluded that intake of Linum usitatissimum and Perilla frutescens as sources of omega-3 fatty acids will be beneficial for preventing cancer.