• Toxicological Research
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• v.17 no.2
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• pp.151-157
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• 2001

Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effect of HM 10411 was examined on neutropenia caused by anticancer agents. Neutropenia in normal ICR mice was induced by a single combined intraperitoneal injection of 130 mg/kg of cyclophosphamide (CPA). 4.5 mg/kg of doxorubicin (DXR). and 1 mg/kg of vincristine (VCR) on day O. Neutropenia in tumor-bearing mice was made by a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CPA) into BALB/c mice bearing Colon 26 adenocarcinoma at 7 day after tumor implantation. HM 10411 or filgrastim (100 $\mu\textrm{g}$/kg/day) was subcutaneously administered for 5 consecutive days starting 1 day after injection of anticancer agents in order to stimulate neutrophil production. Injection of HM 10411 accelerated the recovery from these anticancer drug-induced neutropenia. In normal and tumor-bearing mice. neutrophil production efficacy of HM 10411 was similar than that of filgrastim. These results suggest that HM 10411 could be useful in the clinical treatment for neutropenia induced by anticancer agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.47-54
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• 2014

The aim of this study is to evaluate the effects of green tea polyphenol (GTP) on anticancer treatment with cisplatin (CP), using both an in vitro cell culture model and an in vivo mouse model of established breast tumor. Mouse breast cancer cells (EMT6) were treated with or without GTP and CP followed by determination of the cell viability using an MTT assay. The relative cell viability of CP treated EMT6 cells was 96% at a 20 ${\mu}g/mL$ concentration of cisplatin; however, in combination with GTP (50 ${\mu}g/mL$), the cell viability decreased to 20% at the same concentration of CP (20 ${\mu}g/mL$). For the in vivo study, EMT6 cells were inoculated into Balb/c mice for the establishment of a tumor-bearing mice model. The tumor-bearing mice were treated with CP (5 mg/kg. i.p.) with or without dietary GTP (0.2% drinking water). Tumor growth was monitored by a measurement of tumor size using a digital caliper, and nephrotoxicity was determined by enzymatic and histological examinations. The levels of p53 and caspase-3 in tumor tissues were examined by a Western blot. In tumor-bearing mice treated with GTP plus CP, the increment of tumor volume showed a significant reduction, compared with CP or GTP alone. The levels of p53 and cleaved caspase-3 (caspase-3/p17) in tumor tissues of tumor-bearing mice were increased by CP and GTP compared to CP alone. In CP treated tumor-bearing mice, ${\gamma}$-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) activities were decreased, and marked tubular necrosis and dilatation were observed in the kidney. CP-induced enzymatic and histopathological changes in the kidney of tumor-bearing mice were reduced by combinations of GTP with CP. The results of these experiments demonstrated that dietary GTP has a potentiating effect on CP anti-tumor activity and a protective effect against CP-induced renal dysfunction. Therefore, GTP may be used as a modulator in anticancer treatment with CP.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• YAKHAK HOEJI
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• v.45 no.5
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• pp.557-564
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• 2001

To determine effects of zinc on lipopolysaccharide (LPS)-induced production of proinflammatory cytokines and Iymphokines in tumor-bearing ICR mice, this study has been investigated. Zinc chloride (Zn) at doses of 1 mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS greatly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, in both serum and splenic supernatants compared with those in controls. However Zn strongly decreased LPS-increased production of TNF-$\alpha$ and IL-1$\beta$ in spleenic supernatants compared with those in controls and insignificantly also reduced in serum. LPS insignificantly decreased IL-2 levels in spleenic supernatants compared with those in controls but significantly increased interferon (IFN)-${\gamma}$ levels. Zn didn't affect IL-2 production in splenic supernatants compared to controls but significantly enhanced the LPS-decreased production of IL-2. Zn significantly increased IFN-${\gamma}$ levels in splenic supernatants compared to controls and did not affect the LPS-increased production of IFN-${\gamma}$. These findings suggest that Zn may strongly attenuate the LPS-induced pathogenesis of proinflammatory cytokines in tumor-bearing state and significantly up-regulate the LPS-induced function of T cells to produce IL-2 with maintaining normally the LPS- increased levels of IFN-${\gamma}$.

• Applied Biological Chemistry
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• v.51 no.4
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• pp.294-298
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• 2008

Effects of endosulfan (EN), an insecticide, and bleomycin (BL), an antibiotic, on the body weight in the normal mice, and the in vivo cell growth, tumor weight, and hematological parameters of the Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice Mus musculus were evaluated. EN and BL were respectively administered orally and intraperitoneally to the experimental mice; the control group consisted of EAC cell-bearing untreated mice only. EN reduced the body weight in normal mice, whereas BL resulted in a steady body weight compared to the control. EN increased the EAC cell count significantly by reducing the growth of normal viable cells. In contrast, BL reduced the cell count by increasing the proportion of viable cells in the body. The tumor weights induced by EN were significantly higher than those of the EAC control and the BL-treated animals. In comparisons with the control and the BL mice, hematological parameters such as hemoglobin (%) and the number of RBC and lymphocytes were lowered, while counts of WBC, neutrophils, and monocytes were elevated after EN treatments. These results show that BL is capable of reducing the EN-induced neoplastic and haematological alterations in the mice under laboratory conditions.

• YAKHAK HOEJI
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• v.59 no.4
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• pp.164-169
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• 2015

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.736-740
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• 2007

Acanthopanax sessiliflorus SEEM extracts(AS) have been used to treat patient with diseases including cancer in Oriental countries. Recently, AS was known to have anti-cancer and immuno-stimulating activites. For these reasons, we investigated the effects of AS following gamma-ray irradiation on cytotoxicity for solid tumor cell line (S-180) and immune-potentiating ability such as proliferation of thymocytes and splenocytes. Finally we also investigated tumor weight and survival rate in tumor bearing mice. In our results, Treatment with AS suppressed proliferation of solid tumor cells (S-180) effectively. Treatment with AS accelerated thymocyte and splenocyte proliferation in tumor bearing mice. In addition, Treatment with AS reduced tumor weight and prolonged life of tumor bearing mice. In conclusion, we demonstrate that AS following gamma-ray irradiation is useful to treat patients with cancer, and also demonstrate that AS have both direct cytotoxic ability for cancer cells and indirect immune-stimulating action for thymocytes and splenocytes.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.2
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• pp.20-52
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• 1999

In order to investigate the effect of Naetakchungumsankamibang(NTCGS) water extract on the skin tumor induced by 3-MCA and immunological responses in mice, the cytotoxicity against SK-MEL-2 cells and total number of tumors induced by 3-MCA were measured. The numbers of WBC, platelets and RBC, plaque forming cells, hemagglutinin titer, hemolysis titer, carbon clearance, proliferation of splenocyte by thymidine uptake assay, splenic leukocyte by FACS analysis and $TNF-{\alpha}$ were also measured for the evaluation of the immunological responses. The results were obtained as follows: 1. In cytotoxicity against SK-MEL-2 cells, concentration inhibiting cell growth up to below $20\%$ of control was recognized at 1mg/ml of NTCGS. 2. In Inhibitory effect on the skin tumor induced by 3-MCA, the results showed a strong inhibitory effect of NTCGS. 3. In hematological changes in the tumor bearing mice, the numbers of WBC decreased significantly in NTCGS treated group as compared with control. 4. In hematological changes in the tumor bearing mice, the numbers of platelets increased significantly in NTCGS treated group as compared with control. 5. In hematological changes in the tumor bearing mice, the numbers of RBC increased with no significance in NTCGS treated group as compared with control. 6. Effects of the plaque forming cells in the tumor bearing mice, NTCGS treated group exhibited a significant effect compared with control. 7. In terms of the effects on hemagglutinin titer, NTCGS treated group showed higher level than control, without significance. 8. In terms of the effects on hemolysis titer, NTCGS treated group showed higher level than control, without significance. 9. In terms of the effects on phagocytic index K in Balb/C mice, NTCGS treated group showed significant difference from control. 10. In terms of the effects on proliferation of splenocyte by thymidine uptake assay, NTCGS showed significant effect at the concentration of 0.5mg/ml. 11. In terms of the effects on splenic leukocyte of Balb/C mice by FACS analysis, NTCGS treated group showed significantly higher level of helper T cell, B cell and macrophage than in control. 12. In terms of the effects on the secretion of $TNF-{\alpha}$, the treated group showed significant effect at the concentration of 1mg/ml of NTCGS. Based on the results summarized above, NTCGS is considered to have antitumor activity and immunological responses against skin tumor, and to be usable fur the treatment.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.998-1001
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• 2002

Potential antitumor activity of Lactobacillus plantarum cytoplasm was examined using F9 teratocarcinoma-bearing BALB/C mice. The cytoplasmic fraction of L. plantarum was separated by sonication followed by ultracentrifugation. The fraction at a dose of 100 or 200 mg/kg/day was orally administered for 7 consecutive days before or after tumor inoculation to 16 mice. As a control, heat-killed whole cell was used at a dose of 100 mg/kg/day. Upon oral administrations of both the cytoplasm and heat-killed whole cell, when performed after and before tumor inoculation, the survival of F9-bearing mice prolonged more effectively. Administration of the cytoplasm after tumor inoculation extended the average survival days by 30 and $40\%$ at daily dosages of 100 and 200 mg/kg/day, respectively. This result suggests that the cytoplasmic fraction of L. plantarum has strong antitumor activity against mouse F9 teratocarcinoma in vivo.

• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.77-81
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• 1988

Tumor localizing properties of $^{67}Ga$ citrate and $^{169}Yb$ citrate were studies with sarcoma 180 bearing mice. To compare precisely the accumulation of $^{67}Ga$ citrate and $^{169}Yb$ citrate in tumor tissue itself, $^{67}Ga$ and l63yb were administered simultaneously as a mixture of same chemical form of citrate. The yield of $^{169}Yb$ labeled citrated and the of radiopharmaceuticals purity was identified more than 90% by chromatography on silica gel plates. $^{67}Ga$ and $^{169}Yb$ were injected into mice and the mice were killed at 3, 24, and 48 hours following intraperitoneal injection of the radiopharmaceuticals. The retention value of $^{67}Ga$ and $^{169}Yb$ in tumor was similar but they differ from each other markedly in normal tissue distribution. $^{169}Yb$ citrate is cleared up from blood more rapidly than $^{67}Ga$ citrate, and a high tumor to blood ratio is achieved shortly after injection.