• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2006년도 춘계학술대회
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• pp.83-88
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• 2006

In this study we examined the potential for the synergistic augmentation of the activity of inflammatory mouse peritoneal macrophages by stimulation with RGAP combined with IFN-$\gamma$. The moderate augmentative effect induced by preincubation with RGAP was observed in the production of IL-1, IL-6 and NO but not TNF-$\alpha$. In addition, IFN-$\gamma$ had a low activating effect. Following preincubation with both RGAP A and IFN-$\gamma$, a marked enhancement of secretory activity and tumoricidal activity was noted in mouse peritoneal macrophages. Treatment of peritoneal macrophage with combination increased the generation of IL-1, IL-6, TNF-$\alpha$ and NO, whereas the production of reactive oxygen species were not altered. These results demonstrate the synergistic effects on macrophage function of RGAP in combination with IFN-$\gamma$ and suggest that the ability of IFN-$\gamma$ to prime macrophages to produce secretory molecules in response to RGAP may have implications for immunotherapy with this combination.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4991-4998
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• 2016

Objective: This research was conducted to explore mechanisms behind the potency of quercetin in inhibiting colon cancer induced in an experimental model. Materials and Methods: Forty adult male rats of Wistar strain were distributed into 4 groups; a negative control group, a colon cancer bearing group, a quercetin-treated group and a 5-fluorouracil (5-FU)-treated group. Serum TAG72 and GAL3 levels were quantified by ELISA. Colonic Wnt5a and Axin-1 gene expression was estimated by PCR. In addition, colonic tissues were subjected to immunohistochemical examination of Bax expression and histological investigation of histopathological alterations. Results: Quercetin elicited significant reduction in serum TAG72 and GAL3 levels, in addition to significant suppression of colonic Wnt5a gene expression and amplification of colonic Axin-1 gene expression. Also, it caused moderate positive reaction for Bax in mucosal epithelium. Conclusion: The present research provides experimental evidence about the activity of quercetin in the colon cancer of rats. Inhibitory effects on cancer development might be ascribable to regulatory action on Wnt signaling and induction of apoptosis.

• Advances in Traditional Medicine
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• 제3권2호
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• pp.72-79
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• 2003

The present investigation was undertaken to study whether tumor-associated macrophages of Daltons lymphoma (DL), a spontaneous transplantable T cell lymphoma can be activated to tumoricidal state by alcoholic extract of Tinospora cordifolia (ALTC). In vivo administration of ALTC (200 mg/kg body weight) in DL-bearing mice resulted in an enhanced RNI production and an augmented cytotoxic response of tumor-associated macrophages. Earlier we had reported that DL-bearing mice show a regression of thymus and an enlargement of spleen. In vivo administration of ALTC to DL-bearing hosts resulted in a decrease in the weight of spleen and counts of splenocytes along with an increase in the weight of thymus as compared to control DL-bearing mice. In vivo administration of ALTC in DL-bearing mice also resulted in an increase in the proliferation of splenocytes/thymocytes and BMC. The results of this study indicate that the ALTC upon in vivo administration in DL-bearing shows immuno-modulatory effects and thus may have clinical significance.

• Preventive Nutrition and Food Science
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• 제11권2호
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• pp.105-109
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• 2006

Pinus densiflora belongs to the Pinaceae family which has been widely used for health promoting purposes as folk medicine or as a food. Various curative effects of different parts of the pine have been reported including as a remedy for carcinoma. We examined the effects of pine needle water extracts (PNE) on macrophage function using peritoneal macrophage, pre-osteoclast bone macrophage (Raw 264.7 cell) and brain macrophage (C6 microglia). When peritoneal macrophages were treated with various concentrations of PNE ($1{\sim}100{\mu}g/mL$) for 24 hours, phagocytic activity was significantly increased, whereas it had no effect on tumoricidal activity and NO production. However, the treatment of Raw 264.7 with PNE resulted in the enhancement of NO production at high concentration ($100{\mu}g/mL$). Furthermore, the treatment of C6 with PNE increased the production of NO in a concentration-dependent manner, whereas PNE suppressed NO production in $LPS/IFN-{\gamma}-stimulated$ microglia. These results suggest that PNE has differential immunomodulatory effects on macrophages.

• Food Science and Biotechnology
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• 제18권1호
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• pp.218-222
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• 2009

Ability of water extract from Prunella vulgaris Labiatae to stimulate immune system and inhibit tumor metastasis in mice was assessed. In experimental lung metastasis, prophylactic intravenous (i.v.) administration of water extract from P. vulgaris significantly inhibited lung metastasis in a dose-dependant manner. Peritoneal macrophages stimulated with P. vulgaris produced various cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-12 as well as induced tumoricidal activity. In an assay for natural killer (NK) cell activity, i.v. administration of P. vulgaris significantly augmented NK cytotoxicity. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of P. vulgaris on lung metastasis of colon26-M3.1 cells. These data demonstrate that P. vulgaris activate innate immune system to inhibit the growth of foreign materials including tumor cells in mice.

• 약학회지
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• 제45권6호
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.

• Radiation Oncology Journal
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• 제38권1호
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• pp.1-10
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• 2020

Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

• Journal of Ginseng Research
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• 제33권2호
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• pp.99-103
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• 2009

The in-vitro immunomodulatory function of murine natural-killer (NK) cells induced by red-ginseng acidic polysaccharide (RGAP) in ovariectomized (OVX) rats was examined in this study. The IL-2-induced NK cell activity was significantly decreased in the OVX rats compared to the sham groups, but the normally induced NK cell activity was not. RGAP, however, increased the NK cell activity in both groups, and this effect involved iNOS expression. The inhibition of iNOS activity did not increase the NK cell cytotoxicity by RGAP in the OVX rats. The data that were obtained also demonstrated that the expression of iNOS was increased in the spleen of the OVX rats. These results indicate that RGAP increases the tumoricidal activity of the NK cell in the OVX rats, which is a primed or activated state of innate immune cells resulting from the changes in cytokine production induced by estrogen-deficient stress. Therefore, RGAP has a synergistic effect on the NK cell activities, which are regulated by the iNOS signals in OVX rats. This suggests that RGAP is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in OVX rats.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1771-1779
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• 2015

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Presently, targeted therapy via monoclonal antibodies to specific tumor-associated antigens is being continuously developed. Hep88 mAb has proven to exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To verify the pathway, we then demonstrated downstream up-regulation of caspase-3, caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated enzyme activity by colorimetric assay. Active caspase-3 determination was also accomplished by flow cytometry. Active caspase-3 expression was increased by Hep88 mAb treatment in a dose-and time-dependent manner. All of the results indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases. These conclusions imply that Hep88mAb might be a promising tool for the effective treatment of HCC in the future.