• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.53-63
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• 2003

This study was analyzed the effects of blood-activating and stasis-eliminating herbs on anti-tumor and hematogenic metastasis. The metastasis and recurrence of tumor was the basis of yudok(yudu) on remained tumor cell and stagnation of blood, thermotoxo, phlegm, asthenia of healthy enerngy, stagnation of vital energy. Malignant tumor is caused by carcinogen and go through the progress of initiation, promotion, progression, it is closely related with Eohyul$(y{\grave{u}}xi {\breve{e}})$. Symptoms of blood stasis disease are purplish tongue, mass, fixed stabbing pain, ecchymosis of nail, hypodermic petechia, dermal thesaurismosis, melena, ecchymoma, disturbance of circulation. Effects on the therapy of activating blood circulation and congestion are anti-tumor, anti-coagulation, anti-hemolysis, anti-solution, anti-inflammation, anti-infection, control of blood circulations, control of connective tissue metabolism and control of immunity. They can directly kill the cancer cells entering the blood circulation, inhibit the formation of tumor embody and reduce the blood hyperviscosity. It is suggested that these herbs can be used to prevent and treat blood metastasis of cancer under the guidance of syndrome differentiation.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.31-40
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• 2009

Purpose: This study was carried out to investigate the anti-tumor metastasis effect and activation of innate immunity by extracts of Mori radicis cortex. Methods: Anti-tumor metastatic experiment was conducted in vitro and in vivo by using colon 26-M3.1 carcinoma cell, L5178Y-R lymphoma cell and HeLa cell. To observe the activation of innate immunity by extracts of Mori radicis cortex, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Mori radicis cortex extracts significantly inhibited tumor metastasis. In an in vitro cytotoxicity analysis, Mori radicis cortex affected tumor cell growth above specific concentration. Mori radicis cortex also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-6, IL-10, IL-12, TNF-${\alpha}$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Mori radicis cortex on tumor metastasis. Conclusion: Mori radicis cortex appears to have considerable activity on the anti-metastasis by activation of innate immunity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1833-1840
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• 2013

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), ${\gamma}$-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.41-52
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• 2009

Purpose: This study was designed to investigate the anti-tumor metastasis by immunomodulating effects of extracts of Prunellae Spica. Methods: Antimetastatic experiment was conducted in vivo by using colon 26-M3.1 carcinoma. And we observed cytotoxicity of Prunellae Spica on colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell and macrophage. To observe the immnomodulating effects of Prunellae Spica, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Prunellae Spica extracts significantly inhibited tumor metastasis in vivo. In an in vitro cytotoxicity analysis, cell growth are closer to 100% in case of colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell at low concentration. In case of macrophage, cell proliferation is closer to 100% less than $62.5{\mu}g/m{\ell}$ of Prunellae Spica extracts. The level of cytokine such as IL-6, IL-10, IL-12 which stimulates Prunellae Spica extracts was increased in dose-dependent manner compared to the control group. TNF-${\alpha}$ is hardly secreted less than $250{\mu}g/m{\ell}$ The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Prunellae Spica on tumor metastasis. Conclusion: Prunellae Spica appears to have considerable activity on the anti-metastasis by activation the immune system such as macrophage and NK cell.

• Molecules and Cells
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• v.43 no.5
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• pp.479-490
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• 2020

Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4⁺ T cells, CD8⁺ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

• Food Science and Biotechnology
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• v.18 no.1
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2681-2684
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• 2014

Aim: To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. Materials and Methods: We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Results: Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Conclusions: Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.522-527
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• 2002

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• The Korean Journal of Food And Nutrition
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• v.26 no.3
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• pp.375-382
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• 2013

The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at $100^{\circ}C$(OeE-100). OeE-100 doses up to $62.5{\mu}g/m{\ell}$ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous ($4{\sim}100{\mu}g/mouse$) or oral (2 mg/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-${\alpha}$, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 ($10{\sim}100{\mu}g/mouse$) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 ($100{\mu}g/mouse$) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.