• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.245-251
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• 2015

Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-${\alpha}$) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-${\alpha}$ (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP), and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE-IFN-${\alpha}$ group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-${\alpha}$ group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-${\alpha}$ combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. Conclusions: The use of the TACE and IFN-${\alpha}$ combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.138-147
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• 2003

Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

• Toxicological Research
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• v.3 no.1
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• pp.45-53
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• 1987

A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.

• Advances in Traditional Medicine
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• v.2 no.1
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.448-454
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• 2000

Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

• Journal of Periodontal and Implant Science
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• v.26 no.1
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• pp.216-229
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• 1996

Interferon(IFN) is a sort of glycoproteins that are produced by activated lymphocyte, monocyte and fibroblast. IFN has anti-viral effects, immuno-defensive mechanism and regulating properties to the several kinds of cells that includes affect on the bone formation and resorption. The effect of IFN on the osteoclast & other tissue cells has been studied in a number of researchers with the limited reports on the osteoblast. The purpose of this study was to evaluate the effects of IFN on the osteoblastic function. The MC3T3/El cell(Mouse osteoblast) was incubated in ${\alpha}-minimum$ essential medium containing 10% FBS. To detect the cytotoxic effect of $IFN-{\gamma}$ on osteoblast, the cells were cultured in 96-well plate to which $IFN-{\gamma}$ of various concentrations were added for 2 days. After staining with trypan blue, total cells and living cells were counted under microscope. To determine the activity of alkaline phosphataset(ALP), various concentrations of $IFN-{\gamma}$ were treated to culture medium, and biochemical assay was performed. $IFN-{\gamma}$ and $IFN-{\gamma}$ plus cycloheximide were added to culture medium separately and then ALP activity were determined. To detect the effect of the $IFN-{\gamma}$ on the bone formation of osteoblast, long-term culture was performed, and calcified nodule formation were observed using von Kossa's staining. After the addition of $IFN-{\gamma}$ with various concentrations to the medium, no cytotoxic effect of $IFN-{\gamma}$ was detected at any concentration. The significant increase in ALP activity of osteoblast were found the concentration of $IFN-{\gamma}$ 500-2500U/ml and the culture time of 24-48 hours respectively. The enhancement of ALP activity by $IFN-{\gamma}$ of osteoblast was decreased significantly by the treatment of cycloheximide. After long-term culture of osteoblast, the nodule formation was found to be increased in number and density by the addition of 500 U/ml $IFN-{\gamma}$. These results suggest that $IFN-{\gamma}$ was affected on the bone formation of osteoblast. Forthemore this kind of study or $IFN-{\gamma}$ to osteoblast will be held continuously.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.16-27
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• 2004

In the traditional Chinese medicine, Drynariae Rhizoma (DR) has been reported as a good enhancer for bone healing. DR, a plant widely used in the traditional medicinal systems of Korea, has been reported to possess antiviral, antibacterial and anti-inflammatory activities. Modulation of immune response to alleviate disease has been of interest for a long time. Plant extracts have been widely investigated for possible immunomodulatory properties. Thus, I have evaluated the anticellular and immunomodulatory properties of ethanolic extract of DR. DR extract inhibited proliferation of mitogen (phytohaemagglutinin; PHA) and antigen (purified protein derivative; PPD)-stimulated human peripheral blood mononuclear cells (PBMCs). In addition, DR inhibited growth of several cell lines of mouse and human origin. It also inhibited production of nitric oxide (NO), interleukin-2 (IL-2) and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. Intracytoplasmic $interferon-{\gamma}\;(IFN-{\gamma})$ and expression of cell surface markers, CD16 and HLA-DR, on human PBMC, were not affected on treatment with DR but CD25 expression was down regulated. This study demonstrates the antiproliferative and immunosuppressive potential of ethanolic extract of DR in vitro.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.1
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• pp.1-9
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• 2017

Acer tegmentosum Maxim (ATM) is known as traditional medicine for treatment of hepatic disorders such as hepatitis, related-inflammatory disease, and hepatic cancer. In this study, we evaluated the antioxidant and anti-inflammatory effects of ATM extracted with $80^{\circ}C$ water or 95% ethanol. Antioxidant activities of ATM extracts were measured based on DPPH and ABTS radical scavenging activities, total polyphenolic compound contents, and ferric reducing antioxidant power. The anti-inflammatory effects of ATM extract were assayed on release of nitric oxide, tumor necrosis factor $(TNF)-{\alpha}$, and interferon $(IFN)-{\gamma}$ from lipopolysaccharide (LPS)-induced macrophages. In these experiments, 95% ethanol extract of ATM showed stronger antioxidant and anti-inflammatory effects than water extract. Therefore, we determined the effects of ATM ethanol extract on an animal model of sepsis. Seven days oral gavage of ATM ethanol extract followed by LPS stimulation reduced the protein levels of $TNF-{\alpha}$ and $IFN-{\gamma}$ in serum as well as mRNA levels of $TNF-{\alpha}$ and interleukin-6 in intestinal epithelial cells. In addition, ATM ethanol extract reduced DNA damage in mouse lymphocytes. These results indicate that ATM extract has strong antioxidant and anti-inflammatory in vitro and in vivo effects and may be developed as a potential food material for prevention of inflammatory diseases.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.70-74
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• 2013

L-ascorbic acid (vitamin C) is one of the well-known antiviral agents, especially to influenza virus. Since the in vivo antiviral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-${\alpha}/{\beta}$, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-${\alpha}/{\beta}$, were increased in the lung. Taken together, vitamin C shows in vivo antiviral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-${\alpha}/{\beta}$.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.