• Molecules and Cells
• /
• 제42권12호
• /
• pp.869-883
• /
• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• 대한한방내과학회지
• /
• 제25권2호
• /
• pp.183-194
• /
• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models against 3LL cell lines. Soonkiwhajungtang may only mimic direct anti-tumor effects against 3LL cell lines, but signs of worsening induced by implantation of tumor cell lines generally decreased, while the total WBC and lymphocyte numbers increased. Therefore, experimentation suggests that Soonkiwhajungtang extracts reduced the critical toxicity of doxorubicin, and that Soonkiwhajungtang extracts have favorable synergic effects when combined with doxorubicin.

• 대한한방부인과학회지
• /
• 제22권1호
• /
• pp.41-52
• /
• 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.

• Clinical and Experimental Pediatrics
• /
• 제53권11호
• /
• pp.975-978
• /
• 2010

A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-${\alpha}$ immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-${\alpha}$ for pediatric PEComa of the colon.

• Journal of Ginseng Research
• /
• 제35권3호
• /
• pp.315-324
• /
• 2011

This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without $100{\mu}g/L$ PMA in the absence or presence of various concentrations (100, 200, or $300{\mu}g/mL$) of red ginseng extract. Red ginseng extract treatment caused signifi cant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were signifi cantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity signifi cantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.

• Journal of Acupuncture Research
• /
• 제23권6호
• /
• pp.61-76
• /
• 2006

To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of herbal-accupunture with Orostachys japhonicus A.Berger, infusion solution put into Kansu(BL18) of mouse induced by Colon26-L5 human colon cancer cells, which are corresponding to humanbody. We observed the change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen and kidney, histological analysis on tissue metastasis of liver, splenic cell proliferation, the expression of cytokine gene, the number of CD4+, CD8+, CD9+ and NK cell, and concluded like this. The results were obtained as follows ; 1. In acute and sub-acute cytotoxicity experiment, significantly signs were not appeared in all groups. 2. Antimetastatic experiment in vitro and in vivo showed that Orostachys Japhonicus A.Berger Herbal-acupuncture at Kansu(BL18) has antimetastatic effects. 3. The spleen cells proliferation of the experimental groups treated with Orostachys Japhonicus A.Berger infusion solution extract has increased significantly compared with that of the control group. 4. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. 5. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Above the results revealed that herbal-accupunture with Orostachys Japhonicus A.Berger infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

• 생약학회지
• /
• 제38권2호통권149호
• /
• pp.117-122
• /
• 2007

The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology. Whole tumor Iysates have been used either alone or combined with adjuvants to induce specific immune response in vivo. Here, we examined whether freezing/thawing (F/T) colon26-M3.1 tumor cell admixed with EN-3, glycoprotein purified from Acanthopanx Senticosus, could stimulate in vivo immunity by using a murine experimental tumor metastasis model produced by colon26-M3.1 carcinoma cells. Vaccination of mice with F/T treated colon26-M3.1 carcinoma cells in combination with EN-3 as an adjuvant resulted in a significant inhibition in tumor metastasis of mice against live colon26-M3.1 carcinoma challenge. In addition, the splenocytes from vaccinated mice exhibited a higher proliferating activity and secreted interferon-${\gamma}$. These results suggest that EN-3 can be applied to immunoadjuvant to enhance the antitumor immunity in vivo.

• 동의생리병리학회지
• /
• 제22권2호
• /
• pp.282-289
• /
• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• 동의생리병리학회지
• /
• 제20권5호
• /
• pp.1285-1289
• /
• 2006

Hominis placenta (HP) has been used as an agent for promoting physiological function in traditional asian medicine. The present study was peformed to investigate whether HP acupuncture treatment in an experimental tumor mice model inhibit tumor growth through immunomodulatory effects. Mice were inoculated subcutaneously with colon26-L5 cells on the back. Three days after tumor inoculation, HP herbal acupuncture treatment was conducted on BL18 acupoint every other day for three weeks. HP Herbal acupuncture treatment significantly suppressed the primary tumor growth and prolonged survival rate. To evaluate immunomodulatory effect of HP acupuncture, splenocytes proliferation assay, fluorescence-activated cell sorting (FACS) and ELISA for IFN- ${\gamma}$, and IL-4 cytokine level. HP herbal acupuncture enhanced the mitogenic activity of Balb/c whole splenocytes induced by various mitogenic stimuli and increased immune cell population such as T cell, B cell, Th cell, Tc cell and Macrophages. HP herbal acupuncture caused a marked increase of production of Th1 cytokine (IFN- ${\gamma}$ ,) and decrease of production of Th2 cytokine (IL-4). These results indicated that HP herbal acupuncture suppresses tumor growth through a mechanism leading to a Th1 dominant immune state.

• Genomics & Informatics
• /
• 제9권4호
• /
• pp.173-180
• /
• 2011

Recent trends in generating multiple, large-scale datasets provide new challenges to manipulating the relationship of different types of components, such as gene expression and drug response data. Integrative analysis of compound response and gene expression datasets generates an opportunity to capture the possible mechanism of compounds by using signature genes on diverse types of cancer cell lines. Here, we integrated datasets of compound response and gene expression profiles on NCI60 cell lines and constructed a network, revealing the relationship for 801 compounds and 341 gene probes. As examples, obtusol, which shows an exclusive sensitivity on a small number of colon cell lines, is related to a set of gene probes that have unique overexpression in colon cell lines. We also found that the SLC7A11 gene, a direct target of miR-26b, might be a key element in understanding the action of many diverse classes of anticancer compounds. We demonstrated that this network might be useful for studying the mechanisms of varied compound response on diverse cancer cell lines.