• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4871-4876
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• 2014

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.3
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• pp.349-354
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• 2014

Elevation of intracellular calcium ($Ca^{{+}{+}}$) triggers degranulation of mast cells by bypassing receptor activation. Flos Sophora japonica L. has been used as a natural dying source and has been reported to have biological activities such as anti-inflammatory and anti-allergic effects through $Fc{\varepsilon}RI$ and IgE crosslinking. In the present investigation, we report the regulatory effect of ethanolic extract of Flos Sophora japonica L. (S.F) on allergic mediators produced by $Ca^{{+}{+}}$ ionophore activation in mast cells. S.F significantly inhibited calcium ionophore (A23187)-induced interleukin (IL)-4 and tumor necrosis factor (TNF)-${\alpha}$ production as well as mast cell degranulation. Furthermore, administration of S.F suppressed allergic reactions in a 2,4-dinitrofluorobenzene (DNFB)-induced allergic dermatitis mouse model. Both oral administration and ear painting using 50 mg/kg of S.F significantly reduced levels of cytokines such as IL-4, TNF, and interferon-${\gamma}$ in ear tissues compared to the DNFB alone-treated group. Serum IgE level in the S.F-treated group also decreased compared to the DNFB alone-treated group. Weights of spleens and lymph nodes in the S.F-treated groups also decreased compared to the control group. Considering the data, we conclude that S.F mediates its anti-allergic effects not only through $Fc{\varepsilon}RI$ stimulation but also $Ca^{{+}{+}}$ influx in mast cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.134-149
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• 2016

Objectives : Gal-Geun-Tang (GT) has been described from SANGHAN in Korean traditional medicine and known to act against cold, fever, hypertension, and nasal catarrh. However, little has yet been learned about the effect of GT on immune function. In the current study, in vitro and in vivo immunomodulatory activity of GT (water extract) was investigated.Methods : Water extract of GT induced in vitro proliferation of spleen cells and significantly increased their proliferative responses during anti-CD3 activation. Using purified splenic T and B cells, it was revealed that GT has a mitogenic activity to B cells and promotes their proliferation induced by lipopolysaccharide, whereas T cell proliferation was not triggered and GT was rather inhibitory to T cell activation caused by anti-CD3 antibody. In the presence of antigen presenting cells (APC), GT addition resulted in a significant increase of IFNγ and IL-4, but not IL-2, production. However, addition of high concentration (1,000㎍/㎖) of GT led to a marked reduction in T cell cytokine production and under such condition, GT facilitated apoptosis of T cells when examined by flow cytometry with propidium iodide staining.Results : In vivo immunomdulation of GT was also investigated using a mouse model. Following keyhole limpet hemocyanin (KLH) immunization, GT (1 ㎎/day) was orally administered for 9 days. Cell numbers in thymus, spleen and peripheral blood were not altered by GT administration, indicating that such dose is not immunotoxic. Cell numbers in draining lymph nodes (LN) and ex vivo Ag-specific proliferation of LN cells were significantly elevated by GT administration. However, any preferential stimulation of T or B and CD4⁺ or CD8⁺ T cell subpopulations was not observed in a flow cytometric analysis of LN cells. This result shows that GT does not promote in vivo B cell proliferation while GT enhances Ag-specific proliferation of LN cells, unlike what was observed in vitro.Conclusions : For a further understanding of in vivo immunomodulatory activity of GT, ex vivo cytokine production of LN cells obtained from KLH-immunized mice was evaluated. Ag-specific IFNγ production was significantly higher in GT-treated mice when compared to PBS-treated control mice. In contrast, IL-4 production in GT-treated group was comparable to control group unlike to in vitro data. In addition, GT administration did not result in any significant differences in serum levels of Ig (IgM, IgG1 and IgG2a) between GT-treated and control groups. Taken together, these data strongly support that GT promotes immune response, more profoundly type 1 helper T cell (Th1) activity and GT may be applicable for treatment of intracellular parasite infection such as viral diseases.

• Journal of Gastric Cancer
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• v.23 no.3
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• pp.499-508
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• 2023

Purpose: Despite scientific evidence regarding laparoscopic gastrectomy (LG) for advanced gastric cancer treatment, its application in patients receiving neoadjuvant chemotherapy remains uncertain. Materials and Methods: We used the 2019 Korean Gastric Cancer Association nationwide survey database to extract data from 489 patients with primary gastric cancer who received neoadjuvant chemotherapy. After propensity score matching analysis, we compared the surgical outcomes of 97 patients who underwent LG and 97 patients who underwent open gastrectomy (OG). We investigated the risk factors for postoperative complications using multivariate analysis. Results: The operative time was significantly shorter in the OG group. Patients in the LG group had significantly less blood loss than those in the OG group. Hospital stay and overall postoperative complications were similar between the two groups. The incidence of Clavien-Dindo grade ≥3 complications in the LG group was comparable with that in the OG group (1.03% vs. 4.12%, P=0.215). No statistically significant difference was observed in the number of harvested lymph nodes between the two groups (38.60 vs. 35.79, P=0.182). Multivariate analysis identified body mass index (odds ratio [OR], 1.824; 95% confidence interval [CI], 1.029-3.234; P=0.040) and extent of resection (OR, 3.154; 95% CI, 1.084-9.174; P=0.035) as independent risk factors for overall postoperative complications. Conclusions: Using a large nationwide multicenter survey database, we demonstrated that LG and OG had comparable short-term outcomes in patients with gastric cancer who received neoadjuvant chemotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.134-142
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• 2010

Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.17-24
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• 2013

Objectives : This study was to evaluate the single dose toxicity of Persicae Semen (PS) in ICR mice. Methods : Aqueous extracts of PS (Yield = 18.60%) were administered as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) guidelines (2009-116, 2009). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. Results : Amygdalin contents in PS aqueous extracts were detected as $32.50{\pm}5.96{\mu}g/ml$. We could not find any PS extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations up to 2,000 mg/kg in both female and male mice, except for transient and slight loss of locomotion detected in female and male mice treated with 2,000 mg/kg. In addition, pharmacological immunomodulatory effects related findings were also demonstrated in 2,000mg/kg treated female and male mice as hypertrophy and hyperplasia of lymphoid cells in the submandibular lymph nodes. Conclusions : Based on the results of this experiment, the approximate lethal dose (ALD) of PS extracts after single oral treatment in female and male mice were considered above 2,000 mg/kg, respectively. It should be carefully used in clinics because the possibilities of respiratory or neurological disorders were observed when administered over 2,000 mg/kg of PS extract related to amygdalin.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1446-1458
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• 2013

The study assessed the effect of dietary supplementation of leaf meal mixture (LMM) containing condensed tannins (CT) on feed intake, nutrient utilization and performance of sheep infected with Haemonchus contortus. Eighteen adult sheep of similar age and body weight ($25.03{\pm}1.52$) were included in this study and out of these, 12 sheep were infected with single dose of infective third stage larvae of H. contortus at 2,000 larvae per sheep. The experimental sheep were allocated in three different groups' i.e. negative control (NC; no infection), control (C; H. contortus infected) and treatment (T; H. contortus infected+CT at 1.5% of the DM through LMM) and the experiment was conducted for a period of 90 d. The intake of dry matter (DM), organic matter (OM) and digestibility of DM, OM, neutral detergent fibre (NDF) and acid detergent fibre (ADF) were comparable among three animal groups. However, digestibility of crude protein (CP) and ether extract (EE) were significantly (p<0.05) higher in NC group as compared to both C and T groups. Nitrogen (N) retention (g/d or % of N intake) was significantly (p = 0.038) lower in C group as compared to T and NC groups. Daily intake (g/kg $W^{0.75}$) of digestible crude protein (DCP), digestible organic matter (DOM) and total digestible nutrient (TDN) did not differ significantly (p<0.05) in the three groups. Haemoglobin (Hb) and packed cell volume (PCV) were significantly (p<0.001) higher in treatment group as compared to control. The level of Hb and PCV reduced (p<0.001) after 30 days of experimental feeding. CT significantly (p<0.001) reduced serum urea in T group as compared to NC and C groups. Serum proteins differed significantly (p<0.01) among the three groups. The activity of serum enzymes AST, ALT, ALP and LDH were also statistically non significant (p<0.05) among treatments. The weight of abomasal lymph nodes (ALN) in T group was higher (p<0.05) than in C group. Treatment group had lower (p<0.05) total worms and fecal egg count compared to control group. It may be concluded that dietary supplementation of CT through LMM significantly improved the N retention, and inhibited the different developmental stages of Haemonchus contortus in experimental sheep.

• Korean Journal of Veterinary Service
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• v.33 no.2
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• pp.135-141
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• 2010

Bovine brucellosis, an important zoonosis, is diagnosed with serological tests such as the RBT, TAT using inactivated whole bacterial cells or bacterial lipopolysaccharide (LPS) antigen in Korea. However, a strong cross-reaction between Brucella spp. and Yersinia enterocolitica O9 in these tests has seriously complicated the diagnosis of animal brucellosis because Brucella spp. shares common antigenic determinants with Y. enterocolitica O9 in the smooth LPS region. In this study, Brucella-field strains were isolated from Brucellapositive Hanwoo in Kimhae, Korea and outer membrane protein (omp) which has low cross-reaction with Y. enterocolitica O9 and high immunogenicity was extracted from the field strains Then we compared ELISA using the extract with RBT-TAT. Fifteen field strains were isolated from 47 supra-mammary-lymph nodes, which were collected from 18 farms. Isolation rate was 32%. Brucella-specific antigen was identified by performing SDS-PAGE or Western blotting on extracted omp with at 0.5% n-lauroylsarcosine One hundred and ninety-two serum-samples were used in the experiment: 142 negative and 50 positive samples verified by RBT-TAT. According to ELISA results, 127 samples were negative and 15 appeared positive among 142 negatives by RBT-TAT, while 42 samples were positive and 8 were negative among 50 positives by RBT-TAT. Therefore, it showed 89.4% of specificity and 84% of sensi-tivity. Through the current experiments, we could set up an ELISA based on the omp which has low cross-reaction and high immunogenicity and concluded that the omp could be a good material for accurate diagnosis of bovine brucellosis.