• Journal of Microbiology and Biotechnology
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• 제10권3호
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• pp.399-404
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• 2000

The adjuvant effect of a muramyl dipeptide (MDP) derivative, MDP-Lys(L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.)inoculation of $10^4$ viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of $100{\;}\mu\textrm{g}$ of MDP-Lys (L18) and $10^4$ X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys(L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys(L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells ($5{\times}10^5/site$) on the back, mice treated with Vac+MDP-Lys(L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4295-4300
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• 2012

Objective: To investigate the therapeutic potential of human embryonic stem cells (hESCs) as a vaccine to induce an immune response and provide antitumor protection in a rat model. Methods: Cross-reactivity of antigens between hESCs and tumour cells was screened by immunohistochemistry. Fischer 344 rats were divided into 7 groups, with 6 rats in each, immunized with: Group 1, hESC; Group 2, pre-inactivated mitotic NuTu-19; Group 3 PBS; Group 4, hESC; Group 5, pre-inactivated mitotic NuTu-19; Group 6, PBS; Group 7, hESC only. At 1 (Groups 1-3) or 4 weeks (Groups 4-6) after the last vaccination, each rat was challenged intraperitoneally with NuTu-19. Tumor growth and animal survival were closely monitored. Rats immunized with H9 and NuTu-19 were tested by Western blot analysis of rat orbital venous blood for cytokines produced by Th1 and Th2 cells. Results: hESCs presented tumour antigens, markers, and genes related to tumour growth, metastasis, and signal pathway interactions. The vaccine administered to rats in Group 1 led to significant antitumor responses and enhanced tumor rejection in rats with intraperitoneal inoculation of NuTu-19 cells compared to control groups. In contrast, rats in Group 4 did not display any elevation of antitumour responses. Western blot analysis found cross-reactivity among antibodies generated between H9 and NuTu-19. However, the cytokines did not show significant differences, and no side effects were detected. Conclusion: hESC-based vaccination is a promising modality for immunotherapy of ovarian cancer.

• Archives of Pharmacal Research
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• 제20권2호
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• pp.128-137
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• 1997

The effects of cylindan, a polysaccharide isolated from the basidiocarps of Agrocybe cylindracea, on murine sarcoma 180 tumor and murine immune cells were examined after intraperitoneal administration. Cylindan exhibited a marked life extension effect in mice against ascite forms of sarcoma 180 and Lewis lung carcinoma at a dose of 50 mg/kg/day, although it did not show any direct cytotoxicity against sarcoma 180, X5563, and MM46 murine tumor cells. Cylindan increased numbers of bone marrow stem cells as well as peritoneal exudate cells in flow cytometry using monoclonal antibodies. The tumor bearing mice group apparently showed the increase of macrophages and cytotoxic T lymphocytes in mouse spleen cells during the early stage of tumor growth. But during the later stage, the control group decreased immune cells and cylindan restored the decreased immune cells in the tumor bearing mice to the normal level. In non-specific immune response, cylindan stimulated the bacterial phagocytosis and acid phosphatase production in macrophages. It also activated components of the alternative complement pathway and natural killer activity against YAC-1 lymphoma. In number of plasma cells as token of stimulation of the differentiation of B lymphocytes. In cellular immunity, cylindan restored the depressed response of delayed type hypersensitivity in the tumor bearing mice to 60% of the normal level and increased the interleukin-2 (IL-2) responsiveness in the IL-2 dependent CTLL-2 cells. These results suggest that cylindan did not show direct cytotoxic effects on tumor cells but restored the decreased immune response of the tumor bearing mice.

• Mycobiology
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• 제38권2호
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• pp.144-148
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• 2010

$\beta$-Glucans have been known to exhibit antitumor activities by potentiating host immunity by an unknown mechanism. The C-type lectin dectin-1, a $\beta$-glucan receptor, is found on the macrophage and can recognize various $\beta$-glucans. Previously, we demonstrated the presence of $\beta$-glucan receptor, dectin-1, on the Raw 264.7 cells as well as on murine mucosal organs, such as the thymus, the lung, and the spleen. In order to investigate immunopotentiation of innate immunity by $\beta$-glucan, we stimulated a murine macrophage Raw 264.7 cell line with $\beta$-glucans from Pleurotus ostreatus, Saccharomyces cerevisiae, and Laminaria digitata. Then, we analyzed cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6 by reverse transcription-polymerase chain reaction (RT-PCR). In addition we analyzed gene expression patterns in $\beta$-glucan-treated Raw 264.7 cells by applying total mRNA to cDNA microarray to investigate the expression of 7,000 known genes. When stimulated with $\beta$-glucans, the macrophage cells increased TNF-$\alpha$ expression. When co-stimulation of the cells with $\beta$-glucan and lipopolysaccharide (LPS), a synergy effect was observed by increased TNF-$\alpha$ expression. In IL-6 expression, any of the $\beta$-glucans tested could not induce IL-6 expression by itself. However, when co-stimulation occurred with $\beta$-glucan and LPS, the cells showed strong synergistic effects by increased IL-6 expression. Chip analysis showed that $\beta$-glucan of P. ostreatus increased gene expressions of immunomodulating gene families such as kinases, lectin associated genes and TNF-related genes in the macrophage cell line. Induction of TNF receptor expression by FACS analysis was synergized only when co-stimulated with $\beta$-glucan and LPS, not with $\beta$-glucan alone. From these data, $\beta$-glucan increased expressions of immunomodulating genes and showed synergistic effect with LPS.

• 대한한방종양학회지
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• 제3권1호
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• pp.1-27
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• 1997

This study was performed to investigate the effects of Eunwhasagantang and Eunwhasagantangganokyong on the viability of tumor cells in vitro(MTT assay), on antitumor effects after Sarcoma-180 cells transplantation into the peritoneal cavity or left groin, and on decreased immune responses in mice induced by methotrexate. The extracts of its herbal medicines were orally administered for 14 or 21 days. To evaluate the effects of the Eunwhasagantang and Eunwhasagantangganokyong many items such as 50% inhibitory concentration($IC_{50}$), mean survival days, tumor and body weight for antitumor effects, and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity, lymphocyte transformation, productivity of interleukin-2 and phagocytic activity for immune responses were measured in ICR mice. The results were obtained as follows; 1. $IC_{50}$ of Eunwhasagantang treated group was 0.000204mg/ml on SNU-396 and that of Eunwhasagantangganokyong treated group was 0.000103mg／ml on SNU-1, those results indicate that the medicine has high antitumor activity. 2. Mean survival times in Eunwhasagantang and Eunwhasagantangganokyong treated groups were slightly increased with no significance, as compared with the control group. 3. Tumor weight in Eunwhasagantang and Eunwhasagantangganokyong treated group was depressed, as compared with the control group(p<0.01). 4. Body weight in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05). 5. Delayed type hypersensitivity in Eunwhasagantang and Eunwhasagantang-ganokyong treated group was slightly decreased with no significance, as compared with the control group. 6. Hemagglutinin titer in Eunwhasagantang and Eunwhasagantangganokyong treated group was slightly increased with no significance, as compared with the control group. 7. Hemolysin titer only in Eunwhasagantang treated group was significantly increased, as compared with the control group(p<0.01). 8. Rosette forming cells only in Eunwhasagantangganokyong treated group was slightly increased with no significance, as compared with the control group. 9. In the NK cell activity, the ratio of effector cells and target cells of the Eunwhasagantang treated group was significantly increased(p<0.01) in case which the ratio was 100: 1, and that of the Eunwhasagantangganokyong treated group was significantly increased(P<.01, p<0.05) in case which the ratio was 100:1, 50:1, as compared with the control group. 10. Lymphocyte trasnformation in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.01). 11. Interleukin-2 in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05, p<0.01). 12. Phagocytic activity in Eunwhasagantang and Eunwhasagantangganokyong treated group was significantly increased, as compared with the control group(p<0.05). According to the above results, it could be suggested that Eunwhasagantang and Eunwhasagantangganokyong have prominent antitumor effects, and enhance both cellular and humoral immunity.

• Advances in Traditional Medicine
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• 제6권1호
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• pp.12-20
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• 2006

Some natural products are able to inhibit radiation effects and exert an antitumor effect with fewer adverse reactions; however, their antitumor effects are less than those of widely-used synthetic drugs. Propolis is a natural material that has been attracting attention, and we extracted this material with water and investigated the effect of continuous propolis administration on radioactivity-induced reduction of hemocytes, in addition to the antioxidant and antitumor effects of propolis. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100 mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. These cells were considered since they are closely associated with immunity to radioactivity. In a second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), a radical generator. In a third experiment, $1\;{\times}\;10^6$ Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Statistical analysis was conducted using ANOVA for multiple groups. In the three experiments, administration of water-soluble propolis inhibited the reduction of hemocytes caused by whole-body irradiation, showed antioxidant effects against radioactivity, and inhibited tumor growth, respectively. In conclusion, our data suggest that the antioxidant effect of watersoluble propolis inhibits hemocyte reduction caused by whole-body irradiation and enhances immunological inhibition of tumor growth.

• 동의생리병리학회지
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• 제24권1호
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• pp.22-25
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• 2010

Hyangsapyeongwi-san has been used for various gastrointestinal diseases in Oriental medicine. Nevertheless, there is little known to scientific evidence for its efficacy and mechanism. This study was aimed to investigate effects of Hyangsapyeongwi-san in gastrointestinal diseases through the analysis of articles. A total of 15 articles were selected from PubMed, KTKP, and Weipu. The selected articles were analyzed according to three aspects of study types, target diseases and its efficacy, and results of clinical studies. Hyangsapyeongwi-san has positive effects in gastrointestinal disorders, such as prevent gastric mucosal injury, improve hyperacidity and dyspepsia, protect oxidative damage, and antitumor effects and enhance both cellular and humoral immunity. However, it proved insufficient to confirm its efficacy owing to lack of clinical studies of high quality. So, we need well designed studies to verify clinical efficacy of Hyangsapyeongwi-san hereafter.

• 대한한방종양학회지
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• 제3권1호
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• pp.99-128
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• 1997

In order to investigate the effects of Kyegyoksan on antitumor effects after Sarcoma 180 cells transplantation into the peritoneal cavity or left groin in mice, and immune depression in mice induced by methotrexate, the extracts of its herbal medicines were orally administered for 14 or 21 days. Experimental studies were performed for measureance of $IC_{50}$ in MTT assay, mean survival days, tumor and body weights for antitumor effects, delayed type hypersensitivity, hemagglutinine titer, hemolysin titer, rosette forming cells, interleukin-2 productivity, lymphocyte transformation, natural killer cell activity and phagocytic activity for immune responses in the immune depressed ICR mice, and SGOT, SGPT, BUN and creatinine for liver and kidney protective function in SO-rats. The results were obtained as follows: 1. From the results of MTT assay, the Kyegyoksan exstracts for SUN-1 and SUN-C4 were inhibited cell viability. 2. Mean survival time in Kyegyoksan-treated group was slightly increased with no effectiveness, as compared with the control group. 3. Tumor weight in Kyegyoksan-treated group was depressed with the statistical significance, as compared with the control group(p<0.01). 4. Body weight in Kyegyoksan-treated group was incresed with the statistical significance, as compared with the control group(p<0.05). 5. Delayed type hypersensitivity in Kyegyoksan-treated group was slightly incresed with no effctiveness, as compared with the control group. 6. Hemagglutinin titer in Kyegyoksan-treated group was incresed with the statistical significance(p<0.05), but hemolysin titer was slightly incresed with no effectiveness, as compared with the control group. 7. Rosette forming cells in Kyegyoksan-treated group was incresed with the statistical significance, as compared with the control group(p<0.001). 8. Interleukin-2 productivity in Kyegyoksan-treated group was incresed with the statistical significance, as compared with the control group(p<0.001). 9. Lymphocyte transfomation in Kyegyoksan-treated group was incresed with the statistical significance, as compared with the control group(p<0.01). 10. Natural killer cell activity in Kyegyoksan-treated group at E/T ratio 100 : 1 was incresed with the statistical significance(p<0.01), but at E/T ratio 50 : 1 and 10 : 1 was slightly incresed with no effectiveness, as compared with the control group. 11. Phagocytic activity in Kyegyoksan-treated group was slightly incresed with no effectiveness, as compared with the control group. 12. The levels of serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, blood urea nitrogen and serum creatinine in Kyegyoksan-treated group were not effective change, as compared with the control group. According to the above results, it could be suggested that Kyegyoksan have prominent antitumor effects, enhance both cellular and humoral immunity, and have no injury to liver and kidney functions.

• 대한한방종양학회지
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• 제1권1호
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• pp.141-165
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• 1995

In order to investigate the effects of Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang on antitumor effects after Sarcoma-180 cells transplantation into the peritoneal cavity or left groin in mice, and immune responses in mice induced by methotrexate, the extracts of its herbal medicines were orally administered for 14 or 21 days. Experimental studies were performed for measurance of mean survival days, tumor and body weight for antitumor effects, and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and phagocytic activity for immune responses in ICR mice. Following results were obtained : 1. Mean survival time in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly prolonged, as compared with the control group(P<0.010, P<0.005). 2. Tumor weight in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly depressed, as compared with the control group(P<0.050, P<0.050). 3. Body weight in Banhabaekchulcheonmatang-treated group was significantly increased (P<0.050), but in Banhabackchulcheonmatanggamibang-treated group was slightly increased with no effectivenes, as compared with the control group. 4. Delayed type hypersensitivity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.010, P<0.050). 5. Hemagglutinin titer in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.050, P<0.050). 6. Hemolysin titer in Banhabaekchulcheonmatanggamibang-treated group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 7. Rosette forming cells in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 8. Natural Killer cell activity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 9. Phagocytic activity in Banhabaekchulcheonmatanggamibang-treated group group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was increased with no effectiveness, as compared with the control group. According to the above results, it could be suggested that Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang have prominent antitumor effects, and enhance both cellular and humoral immunity.

• 한국균학회지
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• 제23권4호통권75호
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• pp.285-297
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• 1995

영지의 균사체를 분획화하여 ${\beta}-glucan$성 다당류인 ganoderan을 분리한 결과, 12%의 균체외성, 13%의 세포질성, 그리고 75%의 세포벽성 분획으로 각각 수획되었다. 각각의 분획들은 추출 부위와는 상관없이 포도당을 가장 많이 포함하고 있었으며, ${\beta}-glucan$의 특정을 지닌 다당류이었다. Ganoderan의 구성당 및 구성 아미노산은 균사체 추출부위에 따라 상이한 비율을 나타내었다. 이들의 생리적 활성을 검색한 결과, 항 보체 활성은 균체외성이며 수용성인 EXO-WS 분획이 38%로 가장 우수하였으며, 세포벽에서 추출한 알칼리 가용성이며 수용성인 CW-AS-WS 분획이 37%를 나타내었다. 항암활성은 CW-AS-WS 분획이 가장 우수하였으며 94%의 종양 억제율을 보였다. CW-AS-WS 는 평균 분자량 20kD로 80% 의 포도당으로 이루어진 ${\beta}-glucan$성 다당류이다.