• IMMUNE NETWORK
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• v.12 no.6
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• pp.269-276
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• 2012

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

• Applied Biological Chemistry
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• v.40 no.6
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• pp.490-494
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• 1997

Anticarcinogenic activity of astaxanthin-containing egg yolks (designate AEY) was investigated for benzo[a]pyrene (BP)-induced mouse forestomach tumorigenesis initiating regimen. Female ICR mouse (6-7 weeks of age) were housed in polycarbonated cages (5 mice/cage; 20 mice/treatment) in a humidity-and-temperature-controlled facility and permitted free access to water and food. One week later, four and 2 days prior to p.o. treatment with BP (2 mg/0.2 ml corn oil), mice were given 0.2 ml PBS containing 50 mg AEY, 100 mg AEY, 150 mg AEY, or 150 mg CEY. Control mice were only given 0.2 ml PBS. Three days later this sequence was repeated for a total of 4 times. Beginning with the first intubation and continuing thereafter, body weight and food intake were recorded once weekly. All surviving mice were sacrificed 24 weeks after the first dose of BP. Mice treated with AEY developed only about one third as many neoplasms/animal as mice in control or CEY-treated group (p<0.05). Reduction effect of tumor development by AEY was dependent upon doses applied. Tumor incidence was also reduced by AEY treatments, but significantly reduced only by 150 mg AEY treatment when compared to that by control or CEY. Food intake and body weight were not affected by AEY treatment. These results indicate that AEY inhibits tumorigenesis of mouse forestomach induced by BP.

• BMB Reports
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• v.47 no.4
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• pp.215-220
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• 2014

Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model.

• Herbal Formula Science
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• v.13 no.2
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• pp.71-91
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• 2005

A/J mice injected with urethane(1mg/ g of body weight) develop tumors with distinct histological patterns, which are classified as solid and papillary. I divided the mice into 3 groups; control group treatment with saline, BYA group treatment with herbal formula, Bopheyangyoungjeon 0.3g/kg and BYB groups treatment with herbal formula 1.5g/kg. The administration of herbal medicine was done every day for 56 days. The experimental results from herbal medicine treatment were compared to those from a saline-treated control group. Serial sections of the whole lung(150 to 200 sections per mouse) showed solid and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. The number of tumor, in the 8-weeks groups, are decreased in the experimental groups compared to control group. COX-2 protein and IGF- I protein expression was more increased in lung tumors of the control group compared to BYA and BYB groups. These results suggest that Bopheyangyoungjeon extract suppress the carcinogenesis of lung in the A/J mouse.

• Herbal Formula Science
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• v.13 no.2
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• pp.17-40
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• 2005

A/J mice injected with urethane(1mg/ g of body weight) develop tumors with distinct histological patterns, which are classified as solid and papillary. I divided the mice into 3 groups; control group treatment with saline, BA group treatment with herbal formula, Soeuminbojungikgitang 0.4g/kg and BA group treatment with herbal formula 2.0g/kg. The administration of herbal medicine was done every day for 8 weeks. The experimental results from herbal medicine treatment were compared to those from a saline-treated control group. Serial sections of the whole lung(150 to 200 sections per mouse) showed solid and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. The number of tumor, in the 8 weeks group, are decreased in the experimental groups compared to control group. COX-2 protein and IGF- I protein expression was more increased in lung tumors of the control group compared to BA and BB groups. These results suggest that Soeuminbojungikgitang extract suppress the carcinogenesis of lung in the A/J mouse.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.4
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• pp.307-313
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• 2021

Traf4 (Tumor necrosis factor Receptor Associated Factor 4) is a member of the tumor necrosis factor receptor (TNFR) - associated factors (TRAFs) family. TRAF4 is overexpressed in tumor cells such as breast cancer and associated with cytoskeleton and membrane fraction. Interestingly, TRAF4 was localized with tight junctions (TJs) proteins including OCLN and TJP1 in mammary epithelial cells. However, the expression patterns and biological function of Traf4 were not examined in preimplantation mouse embryos although Traf4-deficient mouse showed embryonic lethality or various dramatic malformation. In this study, we examined the temporal and spatial expression patterns of mouse Traf4 during preimplantation development by qRT-PCR and immunostaining, and its biological function by using siRNA injection. We found upregulation of Traf4 from the 8-cell stage onwards and apical region of cell - cell contact sites at morula and blastocyst embryos. Moreover, Traf4 knockdown led to defective TJs without alteration of genes associated with TJ assembly but elevated p21 expression at the KD morula. Taken together, Traf4 is required for TJs assembly and cell proliferation during morula to blastocyst transition.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• Korean Journal of Pharmacognosy
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• v.26 no.3
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• pp.253-258
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• 1995

The purpose of this research was to investigate the effects of petroleum ether extract of Euonymus alatus (EAP) on the proliferation of human tumor cells. EAP inhibited the proliferation of HeLa, Hep G2, KHOS/NP and A431 cells. The cytotoxicity of doxorubicin on human tumor cells and Balb/c 3T3 cells were increased by the combination of EAP. EAP did not affect the proliferation of Balb/c 3T3 cells, mouse spleen cells and human lymphocytes. These results suggest that EAP has the cytotoxicity on human tumor cells without cytotoxicity on Balb/c 3T3 cells, mouse spleen cells and human lymphocytes, and increase the cytotoxicity of doxorubicin.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.39-44
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• 2011

Many reports indicate that $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glycyrrhizae Radix has anti-inflammatory and immunoregulatory activities, whereas reports regarding anticancer activity of the compound are few. In present study, we investigated antitumor effect of $18{\beta}$-GA on tumor caused by A549 cancer cell in mice. Data resulting from the cytotoxicity assay showed that $18{\beta}$-GA caused killing of A549 cells. $LD_{50}$ values of $18{\beta}$-GA were app. 180 ${\mu}M$ and 80 ${\mu}M$, corresponding to 48 hr- and 72 hr-treatments, displaying that the killing activity was more effective as the $18{\beta}$-GA treatment was prolonged. Based on these data, antitumor effect of $18{\beta}$-GA was tested in nude mice. For induction of the tumor, A549 ($3{\times}10^6$ cells/mouse) was injected subcutaneously into the lateral abdomen of nude mice (Balb/c nu/nu). To determine the antitumor effect, nude mice with tumor were given $18{\beta}$-GA (1 mg/200 ${\mu}l$/mouse) intraperitoneally every three days for four times. Tumor-sizes were measured with a caliper for a period of 24 days. Results showed that the $18{\beta}$-GA treatment reduced the tumor-sizes (P<0.05) as compared with negative control nude mice that received diluent (DPBS). The reduction degree was greater than reduction degree by doxorubicin (60 ${\mu}g$/mouse), and the pattern of reduction was almost sustained during the entire period of the observation. In conclusion, our studies demonstrate that $18{\beta}$-GA has antitumor activity to the A549 cancer cell-caused tumor.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.95.1-95
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• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.