• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.743-748
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• 2016

Background: $K^-Ras$ activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. Purpose: To evaluate the impact of cellular genetic makeup of two colon cancer cell lines with different genetic backgrounds, HCT-116 ($K^-Ras^-/p53^+$) and Caco-2 ($K^-Ras^+/p53^-$), on response to potential anti-tumour effects of EA. In addition, the influence of $K^-Ras$ silencing in HCT-116 cells was investigated. Materials and Methods: Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of $K^-Ras$ siRNA or incubated with ellagic acid following transfection. Results: The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce $K^-Ras$ protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected. Conclusions: Cellular genetic makeup ($K^-Ras^-/p53^-$) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant $K^-Ras$).

• The Korean Journal of Food And Nutrition
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• v.22 no.4
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• pp.542-547
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• 2009

Brine mineral water(BMW) has recently gained attention as a new water resource due to its biological activities. In this study, BMW from the Geumjin area(Gangneung-city, Korea) was evaluated for its growth inhibition, anti-metastasis and anti-angiogenesis activity against cancer cells. The in vitro cytotoxicity was measured by CCK assay, and the anti-metastasis activity was estimated by lung metastasis in vivo. The in vitro incubation of mouse splenic cells with BMW that had been diluted more than 4-fold showed no effect on the cell growth when compared to a control group. Additionally, BMW inhibited the growth of the EL-4, L5178Y-R and colon26-M3.1 cancer cell lines in a dose-dependent manner. In vivo evaluation of the anti-metastasis activity of BMW in BALB/c mice inoculated with the colon26-M3.1 cell line revealed dose-dependent inhibition in response to treatment with samples that were diluted by up to 9 times. Finally, treatment with BMW effectively suppressed the growth of vascular endothelial growth factor(VEGF) added human umbilical vein endothelial cells. Overall, these results suggest that BMW has anti-cancer activity.

• Journal of Life Science
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• v.32 no.11
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• pp.882-889
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• 2022

Breast cancer anti-estrogen resistance 3 (BCAR3) has been identified as one of the genes that induces anti-estrogen resistance in breast cancer. We have previously reported that BCAR3 activates promoters of c-Jun, activator protein-1, and the serum response element. In this study, we investigated the functional role of BCAR3 in the activation of the estrogen response element (ERE) in normal human breast MCF-12A cells. Transient expression of BCAR3 induced ERE activation, which was further increased by 17β-estradiol treatment but was not blocked by the anti-estrogen tamoxifen. Next, we studied the signaling pathway of BCAR3 leading to ERE activation. BCAR3-mediated ERE activation was inhibited by LY294002 and AZD5363, inhibitors of the phosphatidylinositol (PI) 3-kinase pathway, but not by PD98059 and U0126, inhibitors of the mitogen-activated protein kinase pathway. ERE activation was induced by the catalytic subunit p110α. of PI3-kinase or the active mutant of Akt, and this activation was not further increased by additional BCAR3 transfection. Based on these results, we propose that BCAR3 plays an important role in ERE activation through the PI3-kinase/Akt pathway in human breast MCF-12A cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1261-1270
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• 2006

This study was done to investigate the effect of anti-cancer, anti-metastasis and immune response improvement of herbal-acupuncture with Evodiae Fructus herbal infusion solution(EF-HAS). To study the effects of anti-cancer, anti-metastasis and immune response improvement of EF-HAS, we injected EF-HAS into Chung-wan(CV12) of C57BL/6 mice implanted intravenously with Bl6-Fl0 melanoma. Then, we have examined the effect on the increasing of spleen cells, the effect on the number of CD25$^+$/CD4$^+$, CD8$^+$/CD3e$^+$, CD69$^+$/B220$^+$, NK1.1$^+$/CD3e$^+$ cells in mice's PBMCs, the effect on the pulmonary colony number, and the effect on median survival time(MST) and increase of life span(ILS) of C57BL/6 mice implanted intravenously with Bl6-Fl0 melanoma. The following results were obtained; in the experiment groups treated with EF-HAS, the spleen cell proliferation in C57BL/6 mice, the percentage of CD25$^+$/CD4$^+$, CD8$^+$/CD3e$^+$, CD69$^+$/B220$^+$, NK1.1$^+$/CD3e$^+$ cells in C57BL/6 mice's PBMCs, and MST and ILS of C57BL/6 mice implanted intravenously with Bl6-Fl0 melanoma were significantly increased compared with that of the control group. And in the experiment groups treated with EF-HAS, the pulmonary colony number of C57BL/6 mice implanted intravenously with Bl6-Fl0 melanoma was decreased significantly compared with that of the control group. These results support a role for EF-HAS might De usefully applied in treatment of cancer.

• Journal of Acupuncture Research
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• v.21 no.5
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• pp.205-218
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• 2004

Objectives : The purpose of this experiment is to study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Carthami Flos infusion solution(CTT-HAS). Methods : We injected Carthami Flos infusion solution into Chung-wan(CV12) of C57BL/6 mouse which is corresponding to human Chung-wan(CV12). We observed its effect on the number of $CD25^{+}/CD4^{+}$, $CD8^{+}/CD3e^{+}$, $CD69^{+}/B220^{+}$, $NK^{+}/CD3e^{+}$ cells in mouse PBMCs, the number of the pulmonary colony, and the effect on MST and ILS of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results Conclusions : 1. The spleen cells proliferation of the sample groups treated with CTT-HAS extract has increased significantly compared with that of the control group. 2. The percentage of the $CD25^{+}/CD4^{+}$, $CD8^{+}/CD3e^{+}$, $CD69^{+}/B220^{+}$, $NK^{+}/CD3e^{+}$ cells in C57BL/6 mouse PBMCs of the sample groups treated with CTT herbal-acupuncture has increased compared with that of the control group. 3. The lung colony number of the sample groups CTT Herbal-acupuncture has decreased significantly compared with that of the control group. 4. MST and ILS of the sample groups CTT herbal-acupuncture have increased significantly compared with those of the control group.

• Korean Journal of Acupuncture
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• v.21 no.1
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• pp.79-93
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• 2004

Objectives and methods : To study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Sinomenii acuti Lignum infusion solution(SAL-HAS), we injected Sinomenii acuti Lignum infusion solution into Joksamni$(ST_{36})$ of C57BL/6 mouse which is corresponding to human Joksamni(ST36). We observed its effect on the number of $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in mouse PBMCs(peripheral blood mononuclear cells), the number of the pulmonary colony, and the effect on MST(mean survival time) and ILS(increase in MST over control) of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results and Conclusions : 1. The spleen cells proliferation of the sample groups treated with SAL-HAS extract has increased significantly compared with that of the control group. 2. The percentage of the $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in C57BL/6 mouse PBMCs of the sample groups treated with SAL-HAS has increased compared with that of the control group. 3. The pulmonary colony number of the sample groups SAL-HAS has decreased significantly compared with that of the control group. 4. MST and ILS of the sample groups SAL-HAS have increased significantly compared with those of the control group.

• Korean Journal of Acupuncture
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• v.20 no.3
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• pp.115-128
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• 2003

Objectives and methods :　Study the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Evodiae Fructus infusion solution, we injected Evodiae Fructus infusion solution into Zusanli(St36) of C57BL/6 mouse which is corresponding to human Zusanli(St36). We observed its effect on the number of $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in mouse PBMCs, the number of the pulmonary colony , MST and ILS of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results and Conclusions : The spleen cells proliferation of the sample groups treated with EDR-HAS extract has increased significantly compared with that of the control group. The percentage of the $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in C57BL/6 mouse PBMCs of the sample groups treated with EDR herbal-acupuncture has increased compared with that of the control group. The lung colony number of the sample groups treated with EDR herbal-acupuncture has decreased significantly compared with that of the control group. MST and ILS of the sample groups treated with EDR herbal-acupuncture have increased significantly compared with those of the control group.

• Journal of Acupuncture Research
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• v.21 no.6
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• pp.85-102
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• 2004

Objective : The purpose of this experiment is to study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Sinomenii acuti lignun infusion solution(SAL-HAS). Methods : We injected Sinomenii acuti Lignum infusion solution into Chung-wan(CV12) of C57BL/6 mouse which is corresponding to human Chung-wan(CV12). We observed its effect on the nunter of $CD25^+/CD4^+$, $CD8^+/CD3e^+$, $CD69^+/B220^+$, $NK^+/CD3e^+$ cells in mouse PBMCs, the number of the pulmonary colony, and the effect on MST and ILs of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results & Conclusions : 1. The spleen cells proliferation of the sample groups treated with SAL-HAS extract has increased significantly compared with that of the control group. 2. The percentage of the $CD25^+/CD4^+$, $CD8^+/CD3e^+$, $CD69^+/B220^+$, $NK^+/CD3e^+$ cells in C57BL/6 mouse PBMCs of the sample groups treated with SAL herbal-acupuncture has increased compared with that of the control group. 3. The lung colony number of the sample groups SAL Herbal-acupuncture has decreased significantly compared with that of the control group. 4. MST and ILS of the sample groups SAL herbal-acupuncture have increased significantly compared with those of the control group.

• Journal of Cancer Prevention
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• v.21 no.3
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• pp.144-151
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• 2016

Background: Immunoregulatory elements have emerged as useful immunotherapeutic agents against cancer. In traditional medicine, Mori folium, the leaf of Morus alba L. (Moraceae), has been used for various medicinal purposes; however, the immunomodulatory effects have not been fully identified. We evaluated the immunoenhancing potential of water extract of Mori folium (WEMF) in murine RAW264.7 macrophages. Methods: RAW264.7 cells were treated with WEMF for 24 hours and cell viability was detected by an MTT method. Nitric oxide (NO) levels in the culture supernatants were assayed using Griess reagent. The productions of prostaglandin $E_2$ ($PGE_2$) and immune-related cytokines was measured using ELISA detection kits. The mRNA and protein expression levels of Inducible NO synthase, COX-2, and cytokines were assayed by reverse transcription-PCR and Western blotting, respectively. The effect of WEMF on phagocytic activity was measured using a Phagocytosis Assay Kit. Results: WEMF significantly stimulated the production of NO and $PGE_2$ as immune response parameters at noncytotoxic concentrations, which was associated with the increased expression of inducible NO synthase and COX-2. The release and expression of cytokines, such as $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6, and IL-10, were also significantly increased in response to treatment with WEMF. Moreover, WEMF promoted the macrophagic differentiation of RAW264.7 cells and the resulting phagocytosis activity. Conclusions: WEMF has the potential to modulate the immune function by regulating immunological parameters. Further studies are needed to identify the active compounds and to support the use of WEMF as an immune stimulant.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.64-73
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• 2002

FDG-PET has potential as an effective, non-invasive tool to measure tumor response to anticancer therapy. The changes in tumor FDG uptake may provide an early, sensitive guide to the clinical and subclinical response of tumors to cancer treatment, as well as functional assessment of residual viable tumor. This may allow the evaluation of subclinical response to anticancer drugs in early clinical trials and improvements in patients management. However, monitoring tumor responses with FDG-PET is still in its infancy. The methods of measurement of FDG uptake are currently diverse and timing with respect to anti cancer therapy variable. Therefore, there is a need for larger-scale trials along with standardized methodology and a collection of reproducibility data. The recent guideline from the European group seems to be the most comprehensive. In future, the combination of morphological and metabolic images may improve the quantitative nature of these measurements by relating tumor viability to total tumor mass. More data on sensitivity and specificity of FDG-PET technique are needed along with continued advancement of PET methodology.